An aortic covered stent system for in situ drug perfusion into a tumor cavity

Abstract

The application provides an aortic covered stent system for in-situ drug perfusion in a tumor cavity, which comprises a stent, a sleeve and a perfusion catheter, and the inside of the stent is formed into a blood flow channel; the sleeve is fixedly attached to the peripheral wall of the stent along the axial direction of the stent, and a drug delivery channel penetrating in the axial direction is defined between the sleeve and the peripheral wall of the stent, the drug delivery channel is physically isolated from the blood flow channel; the perfusion catheter is prepositioned in the drug delivery channel in a gap fit manner, the head end of the perfusion catheter is provided with a multi-branch umbrella structure made of a shape memory alloy, the multi-branch umbrella structure is configured to be triggered by body temperature to be unfolded after the head end of the perfusion catheter extends out of the drug delivery channel, and a plurality of side holes are arranged on each branch of the multi-branch umbrella structure, so that the problem of uneven drug distribution and inconsistent tumor wall degradation caused by the traditional scheme relying on passive diffusion is solved.

Description

Technical Field

[0001] This invention relates to the field of covered stent technology, and more particularly to an aortic covered stent system for in-situ drug perfusion within the aneurysm cavity. Background Technology

[0002] Endovascular aortic repair (EVAR) is currently the mainstream minimally invasive treatment for aortic aneurysms and dissections. Existing aortic endovascular stent graft systems typically consist of a metal stent framework and an artificial vascular graft. After deployment, the graft expands radially to anchor, using the graft to isolate the aneurysm cavity from blood flow, thereby reducing aneurysm wall pressure. However, once the aneurysm cavity is completely isolated after stent implantation, systemic intravenous medication is unlikely to achieve an effective therapeutic concentration within the aneurysm cavity, leading to delayed aneurysm wall regression, poor organization of mural thrombi, and a persistent long-term risk of rupture.

[0003] To address the aforementioned issues, existing technologies have attempted to introduce local drug delivery functionality. For example, Chinese patent application CN118370627A discloses a covered stent, which adds an outer membrane to the outside of the stent body, utilizing the interlayer between the outer membrane and the main body membrane to form a drug storage space, and allowing the drug to leak out through a drug delivery port on the outer membrane. Although this approach avoids directly creating openings in the membrane and does not require increasing the diameter of the delivery system, it is essentially a passive sustained-release drug delivery system, which suffers from the following insurmountable drawbacks: Drugs in the storage space rely on natural diffusion due to concentration gradients, which cannot generate sufficient fluid pressure to fill irregularly shaped tumor cavities (especially those with large mural thrombi or septa). This can easily create treatment blind spots, prevent three-dimensional drug diffusion, and lead to uneven tumor wall degeneration and an increased risk of long-term rupture. Summary of the Invention

[0004] The purpose of this invention is to address the shortcomings of the prior art by providing an aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity.

[0005] To achieve the above objectives, the present invention provides the following technical solution: A endovascular stent graft system for in-situ drug infusion within the aneurysm cavity includes: A stent, wherein a blood flow channel is formed inside the stent; At least one sleeve is fixedly attached to the outer peripheral wall of the support along the axial direction of the support, and an axially penetrating drug delivery channel is defined between the sleeve and the outer peripheral wall of the support, and the drug delivery channel is physically isolated from the blood flow channel; An infusion catheter is pre-positioned within the drug delivery channel in a gap-fit ​​manner. The tip of the infusion catheter is provided with a multi-branched umbrella-shaped structure made of shape memory alloy. The multi-branched umbrella-shaped structure is configured to unfold upon being triggered by body temperature after the tip of the infusion catheter extends out of the drug delivery channel. Each branch of the multi-branched umbrella-shaped structure is provided with multiple side holes.

[0006] In a preferred embodiment, the number of sleeves is three, and they are evenly spaced at 120° intervals along the circumference of the support body.

[0007] In a preferred embodiment, the inner wall of the sleeve is coated with a hydrogel coating that swells upon contact with blood, which is used to fill the gap in the drug delivery channel after the infusion catheter is withdrawn, thereby achieving self-sealing.

[0008] In a preferred embodiment, the hydrogel coating that swells upon contact with blood consists of a dual-network structure composed of carboxymethyl chitosan and sodium alginate.

[0009] In a preferred embodiment, the austenitic phase transformation end temperature Af of the shape memory alloy is set to 30-35°C, and the multi-branched umbrella-shaped structure is configured to undergo a phase transformation and unfold upon contact with a human body temperature of 37°C.

[0010] In a preferred embodiment, the multi-branched umbrella structure has three branches, and the unfolding angle of the branches is 60°-75°.

[0011] In a preferred embodiment, the side holes are spirally distributed along the branch axis, and the diameter of the side holes gradually increases in the direction away from the tip of the infusion catheter.

[0012] In a preferred embodiment, the support is divided into a covered section and an uncovered section along the axial direction, and the sleeve is located on the outer peripheral wall of the covered section.

[0013] Compared with existing technologies, this technical solution has the following advantages: By setting a multi-branched umbrella-shaped structure at the tip of the perfusion catheter that unfolds based on body temperature, and combining it with side holes designed with spiral distribution and gradient aperture, the drug can be actively sprayed from the distal end to the proximal end of the tumor cavity. The fluid pressure is used to fill the irregularly shaped tumor cavity, which solves the problems of uneven drug distribution, inconsistent tumor wall degradation, and long-term rupture risk caused by the reliance on passive diffusion in traditional methods.

[0014] By utilizing the elastic recoil force of the sleeve itself (physical collapse), the double-network hydrogel coating that expands by 300%-500% upon contact with blood (chemical swelling), and the mechanical squeezing force of the balloon expansion (mechanical compaction), the drug delivery channel is instantly sealed after the infusion catheter is withdrawn, fundamentally eliminating the risk of type II endoleak caused by channel residue and achieving permanent blood flow isolation after EVAR.

[0015] By setting up three cuffs evenly spaced at 120° intervals around the circumference as drug delivery channels, not only is full circumferential coverage ensured during single-channel drug delivery, but redundancy is also provided for long-term postoperative follow-up. Clinicians can selectively repeat perfusion therapy via the spare cuff based on CTA follow-up results, achieving personalized, phased, and dynamic management of the aneurysm healing process and significantly improving long-term efficacy. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity as described in this invention; Figure 2 This is a schematic diagram of the structure of the bracket described in this invention; Figure 3 This is a cross-sectional view of the bracket described in this invention.

[0017] In the diagram: 100 stent, 100a blood flow channel, 110 covered segment, 111 skeleton, 112 covered segment, 120 uncovered segment, 200 sleeve, 200a drug delivery channel, 300 perfusion catheter, 310 multi-branched umbrella structure, 311 side hole. Detailed Implementation

[0018] The following description is intended to disclose the present invention and enable those skilled in the art to implement it. The preferred embodiments described below are merely examples, and other obvious variations will occur to those skilled in the art. The basic principles of the invention defined in the following description can be applied to other embodiments, modifications, improvements, equivalents, and other technical solutions that do not depart from the spirit and scope of the invention.

[0019] Please refer to Figures 1 to 3 The present invention provides an aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity, comprising: Stent 100, wherein a blood flow channel 100a is formed inside the stent 100; At least one sleeve 200 is fixedly attached to the outer peripheral wall of the support 100 along the axial direction of the support 100. An axially penetrating drug delivery channel 200a is defined between the sleeve 200 and the outer peripheral wall of the support 100. The drug delivery channel 200a is physically isolated from the blood flow channel 100a. An infusion catheter 300 is pre-positioned within the drug delivery channel 200a in a gap-fit ​​manner. The tip of the infusion catheter 300 is provided with a multi-branched umbrella-shaped structure 310 made of shape memory alloy. The multi-branched umbrella-shaped structure 310 is configured to extend out of the drug delivery channel 200a after being triggered by body temperature. Each branch of the multi-branched umbrella-shaped structure 310 is provided with multiple side holes 311.

[0020] To address the problem of passive diffusion in the prior art, which cannot fill irregular tumor cavities, this application introduces a multi-branched umbrella-shaped structure 310. After the drug delivery channel 200a extends from the tip of the perfusion catheter 300, this structure automatically unfolds and suspends in the center of the tumor cavity upon being triggered by body temperature. Combined with multiple side holes 311 on each branch, the drug can be actively sprayed uniformly into the circumference and longitudinal direction of the tumor cavity, generating sufficient fluid pressure to fill the irregularly shaped tumor cavity (including the gaps between mural thrombi and septate chambers), achieving three-dimensional drug diffusion and effectively solving the problem of uneven tumor wall degradation and long-term rupture risk caused by passive drug infiltration.

[0021] Because the perfusion catheter 300 is pre-positioned within the axially penetrating sleeve 200 with a gap fit, it provides a structural basis for subsequent catheter removal and for the hydrogel coating on the inner wall of the sleeve 200 to expand and fill the gap upon contact with blood, enabling the system to meet the clinical needs of temporary drug administration and isolation after EVAR.

[0022] like Figure 2 As shown, the stent 100 includes a skeleton 111 and a covering 112. The skeleton 111 is made of nickel-titanium shape memory alloy or cobalt-chromium alloy to form a Z-shaped or mesh structure to provide radial support and achieve anchoring with the blood vessel wall; the covering 112 is made of expanded polytetrafluoroethylene (ePTFE) material with a thickness of 0.1-0.3 mm, and is tightly wrapped around the outside of the skeleton 111 to form a blood flow channel 100a for isolating blood flow.

[0023] The stent 100 is divided into a covered section 110 and an uncovered section 120 along its axial direction, with the length of the uncovered section 120 being shorter than the length of the covered section 110. The covered section 110 refers to the main segment along the stent axial direction that is covered by the covering membrane 112, which forms a stable blood flow channel 100a after implantation. The uncovered section 120 refers to the bare stent segment along the stent axial direction that consists only of the framework 111 and is not covered by the covering membrane 112. It is mainly used to enhance the anchoring friction between the stent and the blood vessel wall, preventing stent displacement.

[0024] like Figure 2 and Figure 3As shown, the sleeve 200 is made of expanded polytetrafluoroethylene flat tubing with a wall thickness of 0.08 mm and a width of 8-12 mm. Its length is approximately equal to the axial length of the covered section 110. The sleeve 200 is fixedly attached to the outer peripheral wall of the covered section 110 along the axial direction of the stent 100, specifically by suturing or using medical adhesive to achieve a fixed connection, thereby ensuring that the sleeve 200 will not shift or peel off during stent release and subsequent catheter withdrawal.

[0025] An axially penetrating drug delivery channel 200a is defined between the outer surface of the sleeve 200 and the membrane 112. This drug delivery channel 200a is independent of the blood flow channel 100a inside the stent 100, and the two are physically isolated by the membrane 112, thereby ensuring that the blood flow barrier is not damaged during drug delivery and fundamentally eliminating the risk of internal leakage caused by the channel penetrating the membrane.

[0026] To further achieve circumferential drug perfusion within the aneurysm cavity, the number of sleeves 200 is preferably three, and they are evenly spaced at 120° intervals along the circumference of the main body of the stent 100. This circumferentially distributed layout ensures that even if only one sleeve 200 is used for drug delivery, the drug can still cover the main area of ​​the aneurysm cavity with the subsequent deployment of the umbrella-shaped structure. At the same time, the remaining two sleeves serve as backup drug delivery channels, supporting repeated interventional treatments at different postoperative periods (such as 1, 3, and 6 months postoperatively), significantly improving the flexibility of clinical treatment and long-term efficacy.

[0027] Preferably, to further achieve instantaneous self-sealing after the infusion catheter 300 is removed, the inner wall of the sleeve 200 is coated with a blood-swellable hydrogel coating. This hydrogel coating consists of a double network structure composed of carboxymethyl chitosan and sodium alginate, with a dry thickness of 0.02mm-0.03mm. It maintains morphological stability during the forming of the sleeve 200 and the compression loading of the stent, without affecting catheter placement and retraction.

[0028] After the perfusion procedure is completed and the catheter 300 is withdrawn, blood enters the lumen of the drug delivery channel 200a and comes into contact with the hydrogel coating. Based on the dual-network cross-linking properties of carboxymethyl chitosan and sodium alginate, the coating rapidly undergoes an ionic cross-linking reaction upon contact with blood (especially calcium ions), resulting in significant volume expansion of 300%-500%. The expanded hydrogel fully fills the gap left after the perfusion catheter 300 is withdrawn and adheres tightly to the inner wall of the sleeve 200 and the outer surface of the membrane 112, thus achieving a microscopic seal. To further enhance the reliability of the seal, a balloon catheter can be introduced through the stent into the corresponding segment of the sleeve 200 for expansion and compaction during catheter withdrawal. The mechanical pressure of the balloon further fills the microscopic gaps with the expanded hydrogel, which, in conjunction with the elastic recoil force of the sleeve itself, forms a triple self-sealing mechanism of physical collapse, chemical swelling, and mechanical compaction.

[0029] The preparation method of the sleeve 200 specifically includes the following steps: A 0.08mm thick expanded polytetrafluoroethylene (ePTFE) membrane is selected and cut into rectangular blanks with a width of 10mm and a length of 130mm. After folding along the long side, the edges are welded using a hot pressing process (380-400℃, 0.3-0.5MPa, 3-5 seconds) to obtain an axially continuous flat sleeve tube blank.

[0030] Preparation of hydrogel coating solution: Weigh 2g of carboxymethyl chitosan, 1.5g of sodium alginate and 0.5g of cross-linking agent genipin, dissolve them in 100ml of purified water, stir evenly to form a uniform and stable hydrogel coating solution.

[0031] The sleeve preform is completely immersed in the hydrogel coating solution, and the system is placed in a vacuum environment (-0.08 MPa) for 10 minutes to allow the coating solution to fully penetrate into the micropores of the expanded polytetrafluoroethylene membrane under capillary action, rather than merely adhering to the surface. After removal, it is immersed in a 2% (w / v) calcium chloride solution for 5 minutes for crosslinking, utilizing Ca²⁺... + The sodium alginate molecular chains are induced to crosslink, and under the action of genipin, carboxymethyl chitosan and sodium alginate form a stable double-network interpenetrating structure. Finally, it is dried in a clean oven at 60°C for 2 hours, which forms a blood-swelling hydrogel coating with a dry thickness of about 0.025 mm on the inner wall of the sleeve 200.

[0032] like Figure 1As shown, the infusion catheter 300 uses a polyurethane tube with an outer diameter of 6 French (approximately 2.0 mm), which has good biocompatibility and bending resistance. The infusion catheter 300 is pre-positioned within the drug delivery channel 200a with a gap fit; specifically, a gap of 0.1 mm to 0.15 mm is maintained on one side between the outer wall of the infusion catheter 300 and the inner wall of the sleeve 200. This gap design ensures smooth pushing and retraction of the catheter within the drug delivery channel 200a and also provides physical space for the subsequent expansion of the hydrogel coating.

[0033] The tip of the infusion catheter 300 (i.e., the end extending into the aneurysm cavity) integrates a multi-branched umbrella-shaped structure 310 made of nickel-titanium shape memory alloy. In a preferred embodiment, this umbrella-shaped structure 310 has three branches, and in the unfolded state, the angle between the branches and the main trunk of the infusion catheter 300 is 60°-75°. The austenitic phase transformation completion temperature (Af point) of the nickel-titanium shape memory alloy is set to 30-35°C, lower than normal human body temperature (37°C).

[0034] It should be noted that, in the initial stage of the release of the covered stent body 100, the multi-branched umbrella-shaped structure 310 and the tip of the perfusion catheter 300 together remain in a closed state and are housed inside the drug delivery channel 200a, adjacent to the opening of the drug delivery channel 200a facing the tumor cavity (i.e., the tip of the sleeve 200).

[0035] During drug administration, the operator first connects the tail end of the infusion catheter 300 to an external high-pressure injection pump to precisely control the drug flow rate and pressure. Then, the infusion catheter 300 is slightly pushed inwards, causing the tip of the infusion catheter 300 and the multi-branched umbrella-shaped structure 310 to move out of the sleeve opening of the drug delivery channel 200a into the tumor cavity. After being released from the constraint of the sleeve 200 and exposed to a body temperature of 37°C, the multi-branched umbrella-shaped structure 310 undergoes a phase transition and automatically unfolds into an umbrella shape.

[0036] To achieve uniform circumferential spraying of the drug within the tumor cavity, each branch of the multi-branched umbrella-shaped structure 310 is provided with multiple side holes 311. As a further preferred embodiment, the side holes 311 are spirally distributed along the axial direction of the branch, and the diameter of the side holes 311 gradually increases from the proximal end to the distal end of the branch (i.e., from near the main trunk of the infusion conduit 300 to away from the main trunk). Specifically, the diameter of the side holes near the main trunk of the infusion conduit 300 is set to 0.3 mm, and the diameter of the side holes away from the main trunk is set to 0.6 mm. This gradient orifice design aims to compensate for pressure loss during fluid flow, ensuring that the outflow rate of each side hole at the proximal and distal ends tends to be balanced, thereby achieving uniform circumferential, blind-zone-free perfusion of the drug from the deep part of the tumor cavity to the proximal side.

[0037] The processing and pre-assembly process of the infusion catheter 300 is as follows: A 6-French outer diameter polyurethane catheter was used, and a nickel-titanium shape memory alloy three-branch umbrella-shaped framework (Af point 35°) was welded to its tip. The three branches of the umbrella-shaped framework were symmetrically distributed with the middle branch being longer and the two sides shorter, measuring 15mm, 20mm, and 15mm respectively. The angle between each branch and the main catheter trunk was controlled between 60-75°. This angle design helps the umbrella-shaped structure form a stable suspension support in the center of the aneurysm cavity after it unfolds. Spiral side holes 311 were machined on the branches using ultraviolet laser to compensate for pressure loss along the flow path and achieve uniform outflow.

[0038] In a Class 10,000 cleanroom environment, the infusion catheter 300 is pre-inserted into the sleeve 200 along the sleeve end direction, with the multi-branched umbrella-shaped structure 310 at its tip adjacent to the opening of the sleeve 200 facing the tumor cavity (i.e., the sleeve tip). Utilizing the martensitic state of the alloy at room temperature, the tip of the infusion catheter 300 is kept straight and coiled and compressed together with the sleeve 200 within the outer sheath 14, at which point the multi-branched umbrella-shaped structure 310 is housed within the drug delivery channel 200a. Finally, the entire assembly, along with the stent, is loaded into the 24French outer sheath, completing the factory pre-installation and eliminating the need for intraoperative superselective cannulation.

[0039] The method of using the aortic endovascular stent graft system for intra-aneurysmal drug infusion is as follows: A channel was established via femoral artery puncture. Under DSA fluoroscopy, a delivery system loaded with a stent 100 and a pre-placed perfusion catheter 300 was advanced to the abdominal aortic aneurysm lesion site. The delivery system mainly includes an outer sheath and an operating handle connected to its proximal end. The stent 100, cuff 200, and perfusion catheter 300 are compressed and loaded within the outer sheath. The operating handle was fixed, and the outer sheath was slowly withdrawn, releasing the stent 100, which radially expands and anchors to the aneurysm neck and distal vessels.

[0040] Connect the external high-pressure infusion pump to the end of the infusion catheter 300. The operator gently pushes the infusion catheter 300 inward, causing the tip of the infusion catheter 300 and the multi-branched umbrella-shaped structure 310 to exit through the opening at the tip of the sleeve 200 into the tumor cavity. After being released from the constraint of the sleeve 200, the nickel-titanium shape memory alloy undergoes a phase change upon contact with the 37°C body temperature, and the multi-branched umbrella-shaped structure 310 automatically opens into an umbrella shape and floats in the center of the tumor cavity. The infusion pump is activated, and the drug is uniformly sprayed circumferentially and longitudinally into the tumor cavity through the side holes 311 on the umbrella-shaped structure 310. The fluid pressure fills the gaps between the mural thrombi and the compartments, achieving full circumferential, blind-zone-free in-situ drug infusion from the distal to the proximal end of the tumor cavity.

[0041] After perfusion, a balloon catheter is introduced into the stent 100 via a guidewire and accurately positioned in the corresponding segment of the cuff 200. The balloon is inflated at a pressure of 10-12 atm and maintained at this inflated state for 15 seconds. While maintaining mechanical compression of the balloon, the perfusion catheter 300 is continuously withdrawn outward until the multi-branched umbrella-shaped structure 310 is completely withdrawn into the drug delivery channel 200a and removed from the body through the tail opening of the cuff 200. After the catheter is withdrawn, blood enters the drug delivery channel 200a. The blood-swelling hydrogel coating on the inner wall of the cuff 200 rapidly absorbs water and expands (expansion rate 300%-500%), filling the gap left by the catheter withdrawal. Simultaneously, the cuff 200 collapses under its own elastic force, combined with the mechanical compaction of the balloon, forming a triple self-sealing mechanism of physical collapse, chemical swelling, and mechanical compaction, effectively blocking blood backflow.

[0042] Depressurize and remove the balloon catheter, then perform angiography to confirm the absence of endoleak and contrast agent extravasation. Postoperatively, perform CT angiography (CTA) at regular intervals (1, 3, 6, and 12 months) to assess thrombosis and wall regression within the tumor cavity. If poor regression is observed, the above drug administration procedure can be repeated using the two reserved spare cuffs (200mm each) to achieve phased, personalized long-term intervention.

[0043] The embodiments described above are only used to illustrate the technical ideas and features of the present invention. Their purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly. The scope of patent application of the present invention should not be limited by these embodiments. That is, any equivalent changes or modifications made in accordance with the spirit disclosed in the present invention still fall within the patent scope of the present invention.

Claims

1. An aortic endovascular stent graft system for in-situ drug perfusion within an aneurysm cavity, characterized in that, include: A stent (100) has a blood flow channel (100a) formed inside the stent (100). At least one sleeve (200) is fixedly attached to the outer peripheral wall of the support (100) along the axial direction of the support (100), and an axially penetrating drug delivery channel (200a) is defined between the sleeve (200) and the outer peripheral wall of the support (100), and the drug delivery channel (200a) is physically isolated from the blood flow channel (100a); An infusion catheter (300) is pre-positioned in the drug delivery channel (200a) in a gap fit manner. The tip of the infusion catheter (300) is provided with a multi-branch umbrella-shaped structure (310) made of shape memory alloy. The multi-branch umbrella-shaped structure (310) is configured to extend out of the drug delivery channel (200a) after being triggered by body temperature. Each branch of the multi-branch umbrella-shaped structure (310) is provided with multiple side holes (311).

2. The aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity as described in claim 1, characterized in that, The number of sleeves (200) is three, and they are evenly spaced at 120° intervals along the circumference of the main body of the support (100).

3. The aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity as described in claim 1, characterized in that, The inner wall of the sleeve (200) is coated with a hydrogel coating that swells upon contact with blood, which is used to fill the gap in the drug delivery channel (200a) after the infusion catheter (300) is withdrawn, thereby achieving self-sealing.

4. The aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity as described in claim 3, characterized in that, The hydrogel coating that swells upon contact with blood consists of a dual-network structure composed of carboxymethyl chitosan and sodium alginate.

5. The aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity as described in claim 1, characterized in that, The austenitic phase transformation end temperature Af of the shape memory alloy is set to 30-35°C, and the multi-branched umbrella structure (310) is configured to undergo a phase transformation and unfold upon contact with a human body temperature of 37°C.

6. The aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity as described in claim 1, characterized in that, The multi-branched umbrella structure (310) has three branches, the branches having an unfolding angle of 60°-75°.

7. The aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity as described in claim 1, characterized in that, The side holes (311) are spirally distributed along the branch axis, and the diameter of the side holes (311) gradually increases in the direction away from the tip of the infusion conduit (300).

8. The aortic endovascular stent graft system for in-situ drug perfusion within the aneurysm cavity as described in claim 1, characterized in that, The support (100) is divided into a covered section (110) and an uncovered section (120) along the axial direction, and the sleeve (200) is located on the outer peripheral wall of the covered section (120).

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