CN120502009A - Flexible endovascular targeted delivery catheter - Google Patents

Abstract

The invention relates to a flexible intravascular targeted delivery catheter which comprises a guide wire rapid exchange section, a puncture needle sheath and a catheter main body which are sequentially connected, wherein the guide wire rapid exchange section is positioned at the front end of the puncture needle sheath, a guide wire exchange channel of a micro guide wire is axially arranged in the guide wire rapid exchange section, an inlet of the guide wire exchange channel is arranged on one end side wall of the guide wire rapid exchange section, which is close to the puncture needle sheath, a delivery pipe is arranged in the catheter main body, three puncture needles which are uniformly distributed along the circumferential direction and are positioned in the puncture needle sheath are connected with the front end of the delivery pipe, three puncture needle outlets are uniformly distributed on the front side wall of the puncture needle sheath along the circumferential direction, a side perfusion pipe is connected with the rear side wall of the catheter main body, a puncture needle pushing device for driving the delivery pipe to push and pull the puncture needle forwards and backwards is connected with the rear end of the delivery pipe, and the rear end of the delivery pipe is penetrated by the rear end of the puncture needle pushing device and is provided with a tail end interface. The catheter can effectively overcome the inherent defects of most of endovascular delivery catheters, and remarkably improves the performance quality of the endovascular delivery catheters and the effectiveness and the practicability of clinical application, thereby showing more superior technical advantages and clinical values in the field of vascular interventional diagnosis and treatment.

Description

Flexible endovascular targeted delivery catheter

Technical Field

The invention relates to a flexible intravascular targeting delivery catheter.

Background

Natural passages of the human body, such as blood vessels, digestive tracts, respiratory tracts, urogenital passages, etc., are regarded as preferred routes of therapeutic drug delivery due to the natural pathway advantages. In clinical practice, the medicine enters into blood vessels through puncture or enters into channels such as digestion, respiration, urinary tract and the like under the guidance of an endoscope, and the clinical curative effect can be greatly improved by combining with the precise medicine release technology. Among the above channels, blood vessels are the most commonly used and critical drug delivery route by virtue of their wide distribution, availability to the whole body and no limitation by organs and tissue structures. In this process, the devices such as intravascular catheters, balloons, and puncture needle-equipped intravascular delivery systems play a significant role. In the field of vascular and neoplastic lesion treatment, the mode of directly delivering the drug to the target site and implementing the local accurate treatment effectively breaks through the limitation of the traditional administration mode, not only remarkably improves the clinical curative effect, but also reduces the incidence rate of systemic side effects. In recent years, with the rapid development of biomedical engineering and drug delivery technology, various methods and devices for local drug delivery in blood vessel cavities have been developed, and a richer and effective scheme is provided for the treatment of related diseases.

Vascular (one) application in lesions

1. The core mechanism of the traditional catheter is that the catheter is accurately delivered to a lesion target blood vessel through an intravascular channel system, and then local drug infusion or embolism treatment is implemented. By virtue of the remarkable minimally invasive characteristics and targeting advantages, the technical system forms a standardized operation range in clinical practice, particularly shows excellent clinical application value in Transcatheter Arterial Chemoembolization (TACE) of solid tumors (such as hepatocellular carcinoma), and becomes a core treatment mode with the most mature technology in the field of tumor interventional therapy and the most abundant evidence of evidence-based medicine.

However, this technical system still has significant limitations at the drug delivery level. After the therapeutic drug is infused through the catheter, although a certain degree of drug enrichment can be achieved in the target organ by means of the first pass effect (first-PASS EFFECT), the retention time of the drug molecules in the focus area shows an exponential decay trend due to the permeability characteristics of the vascular endothelial system and the scouring action of the hemodynamics. Pharmacokinetic studies indicate that the effective concentration of the drug in the local interstitial fluid is maintained for a period of usually no more than 2 hours, and that this brief exposure period is difficult to meet the biological demands of sustained inhibition of tumor cell proliferation or induction of vascular remodeling. More importantly, in the therapeutic scenario of benign vascular lesions such as coronary atherosclerosis or peripheral arterial stenosis, the conventional liquid drug formulation is limited by the molecular surface charge characteristics, lipophilic parameters and the binding capacity with the extracellular matrix of the vessel wall, the trans-endothelial migration efficiency is generally lower than 5%, so that a plurality of drug molecules which show remarkable antiproliferative/anti-inflammatory effects in vitro experiments are difficult to realize effective bioavailability at a target site.

Notably, the drug delivery deficiencies of current interventional therapy systems have derived from multiple clinical challenges. Systemic drug diffusion not only reduces local therapeutic efficacy (bioavailability is typically less than 20%), but is more likely to trigger dose-dependent myelosuppression or organ toxic responses. In addition, the mechanical clearance of the drug attached to the vessel wall by the blood flow shear force, and the drug permeation barrier caused by the lesion vascular endothelial dysfunction, together constitute a key pathophysiological barrier that limits the expansion of interventional therapy to the field of benign vascular disease. Breakthrough of these mechanical drawbacks, a synergistic innovation of new drug carrier systems and accurate delivery technologies is needed.

2. Drug-Coated Balloon as an innovative solution, drug-Coated Balloon (DCB) technology has evolved. DCB adopts special catheter structure design, the surface of the far-end saccule is subjected to nano-level microporation treatment and is loaded with a therapeutic drug-excipient composite coating (drug loading density is 3-5 mug/mm <2 >), and the directional transfer of the drug to the blood vessel wall is realized through the mechanical-fluid coupling effect during saccule expansion. Taking coronary intervention as an example, when an mTOR inhibitor (such as rapamycin) or a microtubule stabilizer (such as paclitaxel) coated on the surface of the saccule contacts a lesion vascular wall, the mTOR inhibitor can act on medium-membrane smooth muscle cells through a double mechanism of passive diffusion and active embedding, so that the rate of cell cycle arrest in the G1 phase is increased to about 70 percent, and the restenosis incidence rate after operation is obviously reduced by 6 months compared with the traditional naked saccule forming operation. The technique has been expanded for clinical intervention in peripheral vascular lesions of the lower extremity arteries (Fontaine IIb-IV phase), renal arteries (stenosis > 70%) and subclavian arteries.

Compared with the traditional Bare Metal Stent (BMS) and Drug Eluting Stent (DES), the DCB has the core advantage of 'interventional non-implantation' characteristic, namely, the DCB realizes the treatment effect through single drug pulse release (half-life period is about 30 seconds) and avoids long-term complications such as late stent thrombus, stent fracture and the like caused by permanent foreign matter retention. However, DCB technology still faces double technical bottlenecks, namely firstly, a drug coating is easily influenced by fluid shearing force and blood vessel wall contact pressure in the balloon conveying process, so that 20-35% of drugs are released prematurely before reaching a target point, secondly, the DCB technology is limited by the existing slow release technology, the effective concentration maintenance time of the drugs in the blood vessel wall is only about 4 weeks, and complex lesions with serious diffuseness and/or calcification are difficult to deal with.

3. Microporous balloon based on the accurate treatment requirement of vascular stenosis/occlusive lesions, a porous topology balloon delivery system (Porous Topological Balloon DELIVERY SYSTEM, PTBDS) has been innovatively developed by the scientific research team. The device carries out bionic reconstruction on the basis of the traditional saccule structure, adopts a porous foam topological structure (the porosity is 65-80 percent, the aperture is 10-50 mu m) to replace the traditional airtight saccule cavity, and the Young modulus (0.5-2.0 MPa) of the device is reduced by 40-60 percent compared with that of the common saccule, so that the contact stress distribution of the blood vessel wall is obviously improved. The core working mechanism of the device depends on the micro-fluidic principle that when the saccule expands at the pressure of 0.5-3atm, the therapeutic agent (medicine/stem cell suspension) realizes the directional permeation of the blood vessel wall through micron-sized through pores (the flow rate is 0.1-0.5 mL/min), and the permeation depth can reach the middle membrane layer (300-500 mu m). Experimental study shows that when PTBDS is used for delivering mesenchymal stem cells, the cell attachment efficiency can be improved to about 80% by regulating and controlling the pore geometry parameters, and the endothelial differentiation rate can reach about 42% by activating the related signal channels. However, due to the limited fluid shear force (> 15 dyn/cm 2) and the lack of extracellular matrix anchoring sites, the loss rate of transplanted cells exceeds 90% after 72 hours, resulting in limited revascularization efficacy.

The technical system also presents a hemodynamic challenge in that the blood flow needs to be completely blocked during balloon dilation (blocking time is often limited to 90 seconds in coronary applications), resulting in a rise in myocardial ischemia score (TIMI frame number) to 28±5 frames (normal <13 frames), a 3.2-fold increase in risk of induced ventricular arrhythmias. To balance therapeutic efficacy with safety, intermittent distension strategies (30 second distension/60 second infusion alternation) are often employed in clinical practice, but result in a decrease in drug permeation efficiency of about 40%.

4. Microneedle catheters, in clinical practice, have two main ways to enhance drug penetration and extend their local residence time. The first approach is to remodel the drug itself, carrying auxiliary active ingredients that enhance permeation/penetration properties. However, because the auxiliary components can potentially inhibit and weaken the target medicament, even destroy the original physical and chemical properties and biological properties of the medicament, the implementation difficulty of the method is high, and the curative effect is difficult to ensure. The second approach is to perform a direct injection through a catheter with a micro-needle at the site where intervention therapy is required. The method is direct and simple to operate, can accurately and targetedly release the medicine into the blood vessel wall or tissues around the blood vessel, prolongs the local retention time of the medicine, and has higher clinical feasibility.

For example, studies have been made on the hiding and inflation-deflation characteristics of globefish's bones, and a smart microneedle coated balloon catheter (MNBC) has been developed. The catheter consists of three layers of coating layers, including a gelatin layer containing Black Phosphorus (BP), a drug carrying microneedle layer and another gelatin layer containing BP. In the uninflated state, the microneedles are hidden under the outermost gelatin protective layer, making the catheter surface relatively smooth for movement within the vessel. Upon reaching the target site, BP converts light energy into heat energy under Near Infrared (NIR) light irradiation, causing the gelatin layer to melt and the microneedles to be exposed and penetrate the vessel wall. Meanwhile, after the gelatin layer of the innermost layer is melted, the micro needle can be separated from the balloon catheter and left in the vascular wall, so that continuous drug release is realized. MNBC has advantages in its responsiveness, penetration ability and biosafety. Through a NIR triggered thermal response mechanism, accurate release of the drug and controllable exposure of the microneedles can be achieved. The design of the micro needle enables the micro needle to penetrate through the vascular wall, the medicine is directly delivered to the lesion part, and the local concentration and the treatment effect of the medicine are improved. In addition, the release function of the micro-needle prolongs the drug release time and further enhances the therapeutic effect.

However, MNBC also faces some challenges. First, the concentration of BP and NIR power have a significant impact on temperature rise, requiring precise control to ensure safety and effectiveness. Second, the mechanical strength and penetration capabilities of the microneedles need to be further optimized to accommodate the needs of different types of vascular lesions. In addition, the biocompatibility and degradation characteristics of BP and gelatin still need to be studied intensively to ensure long-term safety.

Based on this assumption, there are a variety of microneedle puncture catheter devices used for various tests. Such as Binlab retractable microneedle catheters, see figure 1. In fig. 1, the catheter is guided by coaxial guide wire technology (OTW), and three micro-puncture needles (yellow arrows) spaced 120 degrees apart extend through the side holes of the catheter, penetrate the vessel wall, and inject the drug (red arrows). The catheter is pushed to the local part of the blood vessel through the centrally arranged guide wire, and then three micro-puncture needles are arranged in the catheter, so that the nickel-titanium alloy needle with the memory function can be punctured into the wall of the blood vessel, and the aim of locally injecting the medicine is fulfilled.

Another type of injection catheter, designated NIC (needle injection catheter), is used to inject liquid drugs and stem cells into the interior of the myocardium for the purpose of locally repairing the lost myocardium, see figure 2. In the figure 2, three micro-puncture needles with 120-degree intervals are pushed out of a catheter (yellow arrow) by the head end of the catheter, the push of the micro-puncture needles is realized by a spiral pushing device at the tail end of the catheter (red arrow), the catheter is pushed into the heart through a guide tube under C.X line perspective, the micro-puncture needles are unfolded and medicines are injected (yellow arrow), the head end of the catheter is enlarged under X-ray perspective to enable contrast agents injected by the puncture needles to enter the cardiac muscle and generate irregular dispersion areas (annular yellow dotted lines), the heart of an anatomic animal is penetrated into the cardiac muscle, and the external heart model is extended into a heart cavity through the guide tube, and the micro-puncture needles are also extended simultaneously.

When the catheter is used, a guide tube with larger outer diameter is firstly needed to be placed into a target area, then the guide tube is inserted into the catheter, and the micro needle is pushed out by the screw-in device at the tail end to penetrate into the tissue of the target area for injection and treatment. Therefore, the super-selective performance in the blood vessel cavity is poor, and the tortuous tiny blood vessel branches are difficult to enter.

In addition, there is a similar puncture catheter for injecting liquid ablative agent into the peripheral damaged nerve of renal artery to achieve the purpose of treating renal hypertension, see fig. 3. In FIG. 3, A, the catheter is fed into the catheter using coaxial wire (OTW) technique, and B, the micropuncture needle penetrates the renal artery and injects absolute alcohol (Ethanol) to destroy the conductive nerves around the renal artery.

The front end of the injection catheter is provided with 3 micro-puncture needles, each needle is spaced by 120 degrees, the catheter is pushed out, the renal artery is punctured into the adventitia of a blood vessel, absolute ethyl alcohol is injected to damage the sympathetic nerves around the renal artery, mechanical and chemical stimulation signals of the kidney are blocked from being transmitted into the central nervous system, the tension of the sympathetic nerves is reduced, the systemic arterioles are relaxed, and the aim of reducing blood pressure is achieved.

Based on the same device, the channel catheter microneedle can also be used for carrying out targeted injection on the tissue part to be treated with the therapeutic function and manually modifying, separating, purifying and modifying cell components, and can also improve the effects of local retention, permeation and transfection.

5. A microneedle balloon catheter. The design of the catheter combines the characteristics of the saccule and the microneedle, and the saccule and the microneedle are combined together to achieve the aim of penetrating a blood vessel to perform local injection, see figure 4. In fig. 4, the eccentrically designed balloons are folded together (white arrow) and the micropins are wrapped, and after the balloon is inflated, the micropins are released (yellow arrow) and penetrate the target area for drug injection.

The design is mainly characterized in that the balloon is combined with the microneedles, the balloon is designed to be in a foldable state, a combined channel with a plurality of microneedles is wrapped in the combined channel, after the catheter reaches the target area, the balloon is filled, the microneedles are ejected to the surface of the balloon by the balloon so as to penetrate into the inner wall of a blood vessel under the pushing and pressing of the balloon, and therapeutic drugs are injected. Also, stem cells, genes, etc. may be injected to achieve specific local therapeutic objectives.

Application of (II) tumor lesions

The devices and instruments are used for targeted delivery of chemotherapeutic drugs, molecular targeted drugs, ablative agents, gene drugs and the like, and a certain clinical effect is achieved.

In summary, the clinical demands for targeted delivery therapy in the blood vessel lumen are enormous, and the feasibility and clinical efficacy of the scheme are preliminarily verified by the invention of a plurality of catheter apparatuses. However, the existing scheme still has a huge space for iterative upgrade. Such as:

1. The compliance of the catheter is low. It is difficult to reach deeper sites requiring treatment by tortuous slender blood vessels. The catheter designed by the coaxial guide wire technology (Over-the-wire, OTW) is adopted, because the whole catheter needs to be designed with three micro-needles and 4 channels of independent guide wire channels in the middle in parallel, so that the texture of the catheter is relatively stiff and the flexibility is lacked. Therefore, the method is only suitable for the primary branch of the aortic blood vessel, and is difficult to reach for the secondary branch, the far-end blood vessel and the lesion part which is more tortuous in anatomical structure.

The puncture needle has weak puncture ability. Most micro-needles are required to be in an expanded state without deformation, and are generally made of a metal material with a memory function, such as nickel-titanium alloy. The metal has obvious advantages in the aspect of keeping the original prefabricated form, but the material is soft, the micro-needle made of the material is difficult to penetrate through the blood vessel structure with a tough texture, especially the blood vessel structure with an atherosclerosis part, and the clinical practical application effect is not ideal.

The number and distribution of the puncture needles are insufficient. A portion of the balloon encloses the catheter of the micro-needle because the balloon has only a single folding direction. Therefore, when the balloon is unfolded, only a single-direction injection can be performed, and the annular uniform distribution can not be formed around the blood vessel of the target area, so that the curative effect is affected. Secondly, the injection needs to fully fill the balloon, and the micro puncture needle can puncture the blood vessel by the force of the expansion of the balloon. However, filling the balloon may cause blood flow blockage, and may cause myocardial ischemia or even induce arrhythmia, myocardial infarction, etc. in coronary therapy. Thus, the device is also not a perfect solution.

The catheter diameter is larger. As with the first, multiple minimally invasive needles are coaxial (OTW) with the guidewire channel, resulting in larger calibres of the designed and manufactured catheters and difficulty in accessing smaller calibres of blood vessels. In patients with coronary heart disease ischemia or infarction, the lesion part of the patient is often at the part with thinner branches of blood vessels at the deep distal end of coronary artery, the large-caliber catheter is difficult to reach the distal end, and the delivery effect of isolated and purified stem cells, virus transfected stem cells, gene drugs, sustained and controlled release drugs and the like is not ideal.

Balloon design defects. All endovascular delivery devices developed based on balloon inflation principles must be inflated to temporarily block blood flow (typically for 60-180 seconds). In clinical practice, although the duration of the operation process is short, for the vascular stenosis which has insufficient blood supply and has critical hemodynamic compensation (FFR is 0.75-0.80), the severe change of the shear stress of vascular endothelium is extremely easy to be induced, and the risk of iatrogenic vascular injury is obviously increased by 2.8-3.5 times. Therefore, the balloon-based intravascular delivery device has certain design defects, and the balloon-based intravascular delivery device should be fully paid attention to and adopt the measures of optimizing operation steps, reducing use frequency, shortening blocking time and the like as far as possible in clinical application, so that the occurrence of iatrogenic injury is avoided as possible.

The real-time monitoring function design of the radiography channel is lacking. At present, research and development of various intravascular delivery instruments and devices are focused on optimization of injection and delivery efficiency, but an obvious technical short board exists in the key field of intraoperative dynamic evaluation and real-time monitoring, and the lack of the function can cause potential medical risks in clinical practice. From the technical level analysis, performing real-time angiography in operation is an effective solution way, dynamic evaluation and real-time monitoring can be accurately completed, morphological characteristics of blood vessels, such as pathological states of blood vessel interlayer, thrombosis, vasospasm and the like, can be timely and accurately mastered, and further provides a basis for timely intervention for clinicians, so that the method has remarkable advantages in improving operation safety and effectiveness. Therefore, the conveying device is provided with an intraoperative radiography channel, and has extremely important clinical application value.

However, 92% of the instruments lack an integrated design of intraoperative contrast channels, forcing the operator to perform digital subtraction angiography (Digital Subtraction Angiography, DSA) via catheterization (3-5 minutes) after the procedure is completed, where the leak rate of new vascular dissection or acute thrombus can be as high as 15-21%. The hysteresis backtracking type radiography method is difficult to discover and effectively relieve acute complications such as vascular obstruction in time in the drug injection and delivery processes, so that medical risks which cannot be ignored are caused in clinical practice. Because the prior art is difficult to achieve reasonable balance between efficiency optimization and safety guarantee, the prior art directly leads to great challenges of clinical transformation failure and difficult application and popularization after a plurality of intravascular delivery devices undergo a complex research and development process.

Disclosure of Invention

The invention aims to provide a flexible intravascular targeted delivery catheter which can effectively overcome the inherent defects of most intravascular delivery catheters and remarkably improve the performance quality of intravascular delivery catheters and the effectiveness and practicality of clinical application.

The technical scheme includes that the flexible intravascular targeted delivery catheter comprises a guide wire rapid exchange section, a puncture needle sheath and a catheter main body which are sequentially connected, wherein the guide wire rapid exchange section is located at the front end of the puncture needle sheath, a guide wire exchange channel of a micro guide wire is axially arranged in the guide wire rapid exchange section, an inlet of the guide wire exchange channel is arranged on one end side wall of the guide wire rapid exchange section, which is close to the puncture needle sheath, a delivery pipe is arranged in the catheter main body, three puncture needles which are uniformly distributed along the circumferential direction and located in the puncture needle sheath are connected to the front end of the delivery pipe, three puncture needle outlets are uniformly distributed along the circumferential direction on the front side wall of the puncture needle sheath, a side perfusion pipe is connected to the rear side wall of the catheter main body, a puncture needle pushing device for driving the delivery pipe to push and pull the puncture needle forwards is connected to the rear end of the delivery pipe, and the rear end of the delivery pipe is penetrated by the rear end of the puncture needle pushing device and is provided with a tail end interface.

Further, the rear portion of the rapid exchange section of the guide wire has an arcuate connection portion which is connected to the needle sheath so that the axis of the exchange passage of the guide wire is not on the same axis as the axis of the catheter body.

Further, the three puncture needle outlets are uniformly distributed on the front side wall of the puncture needle sheath at intervals of 120 degrees, the puncture needles are in an abduction arc shape, and the three puncture needles are connected with the conveying pipe in the catheter main body cavity through the puncture needle-conveying pipe connecting part.

Further, a guide cone is arranged in the puncture needle sheath and close to the rear end position of the puncture needle outlet, three guide cone holes which are uniformly distributed along the circumferential direction and used for the puncture needle to pass through are axially formed in the guide cone, and the guide cone holes incline outwards from the back to the front.

Further, the puncture needle pushing device comprises a tube body connected to the rear end of the catheter body, a pushing sliding block is connected to the tube body in a sliding mode, the pushing sliding block is provided with a middle connecting portion penetrating into the tube body and fixed to the outer wall of the conveying tube, and a matched sliding limiting structure is arranged between the pushing sliding block and the outer wall of the tube body.

Further, the sliding limiting structure comprises a left limiting groove and a right limiting groove which are arranged on the left side wall and the right side wall of the pipe body, and guide keys matched with the left limiting groove and the right limiting groove in a mortise and tenon mode are correspondingly arranged on the left inner wall and the right inner wall of the pushing sliding block.

Further, the top and the bottom of the pipe body are correspondingly provided with an upper guide rail groove and a lower guide rail groove, the middle connecting part penetrates through the upper guide rail groove and the lower guide rail groove to be fixedly connected with the conveying pipe, and the surfaces of the limiting groove and the guide rail groove are respectively provided with a gradiometer with the mm as a unit.

Further, the middle connecting part is made of high polymer materials and is tightly connected with the conveying pipe, and an anti-slip push button is arranged at the top of the push sliding block.

Further, the front end outer wall of the guide wire rapid exchange section is wrapped with an X-ray-impermeable front end metal marking ring, and the front end outer wall and the rear end outer wall of the puncture needle sheath are correspondingly wrapped with an X-ray-impermeable middle metal marking ring and a rear metal marking ring.

Further, the conveying pipe and the puncture needle are both made of medical steel 440, the tail end connector is coated with a high polymer material layer, a perfusion pipe base is fixed on the side wall of the rear part of the catheter main body, and the side perfusion pipe is communicated with the catheter main body through the perfusion pipe base.

Compared with the prior art, the invention has the following advantages:

1. The flexible endovascular targeted delivery catheter is suitable for clinical medicine, ischemic/neoplastic diseases, atherosclerosis, coronary heart disease, myocardial infarction and vascular interventional therapy.

2. The traditional micro puncture needle catheter adopts a single needle structure, and can only inject the medicine from a single direction, so that the medicine is difficult to uniformly distribute in tissues around blood vessels, and the treatment effect of the medicine is limited.

The invention adopts the multi-needle design of three micro puncture needles, is uniformly distributed at intervals of 120 degrees, can ensure that the medicine is uniformly distributed in the vascular wall and peripheral tissues and realizes the injection and input of local medicine, and for most dose-dependent therapeutic medicines, the design can obviously improve the curative effect of the medicine and optimize the curative effect.

3. Conventional endovascular puncture injection catheters are designed by adopting a guide wire coaxial technology (OTW), and the guide wire and the catheter are in the same channel, so that the diameter of the catheter is thicker, the texture is harder, the rotation operation is not facilitated, and the manufacturing difficulty is increased.

The flexible endovascular targeted delivery catheter of the invention employs a guidewire rapid exchange channel. (1) The catheter can be quickly introduced into a lesion target area, so that the operation difficulty is simplified. (2) The caliber of the catheter main body is reduced, and the coaxial arrangement of the puncture needle and the guiding guide wire is avoided. (3) The rapid exchange channel and the catheter main body are not arranged in parallel, the overall outer diameter of the catheter can be effectively reduced through the distributed structural design, and the smaller outer diameter is beneficial to the smooth entering of the catheter into the blood vessel with smaller caliber, and the manufacturing difficulty of the catheter is remarkably reduced. (4) In the treatment process, the micro-guide wire can be kept in situ, and once complications such as vasospasm, interlayer, obstruction and the like appear, and auxiliary treatment is carried out by other interventional instruments, the micro-guide wire has small caliber and can be well matched with most of treatment instruments, so that rapid exchange operation is convenient to carry out, and the complications appearing in the treatment process are effectively relieved.

4. Conventional injection catheter designs typically employ either the over-the-wire (OTW) technique or lack entirely a guidewire guiding mechanism (e.g., NIC catheters). In this design, multiple metal delivery catheters are arranged coaxially with the catheter sheath and guidewire, resulting in a significant increase in the overall catheter outer diameter. The thick outer diameter limits the application range of the stent in the treatment of the blood vessel cavity, is only suitable for the treatment of large blood vessels such as the primary branch of the aorta, and is difficult to realize for the interventional operation of secondary branches or finer blood vessels.

The invention adopts the design of the single-channel conveying catheter, obviously reduces the manufacturing difficulty of the catheter, avoids complex multi-channel manufacturing and effectively reduces the outer diameter of the catheter. The catheter structure is optimized, and meanwhile, the flexibility of the catheter is ensured, so that the catheter can meet the requirements of the second-stage branch of a large blood vessel and the intracavity treatment of a small blood vessel with a comparable caliber, and the defect of most of the endovascular delivery catheters can be effectively overcome on the premise of keeping the advantages of the existing catheters, so that the quality and clinical use efficacy of the catheters are improved, and the application range of the endovascular treatment is widened.

5. Conventional balloon catheters are injected by inflating the balloon to deploy the micro-needle and penetrate the blood vessel, however, the balloon is inflated and then blocks blood flow, resulting in ischemia at the distal end. If the vessel to be treated has a stenosis or obstruction, the balloon will further exacerbate the distal ischemic symptoms after blocking the blood flow, such as in the coronary artery, and may cause unnecessary surgery-related complications.

When the flexible intravascular targeting delivery catheter reaches a target area for injection treatment, the blood flow is not required to be blocked, so that the continuous smooth blood flow can be kept, and remote ischemia and related complications caused by blocking the blood flow are avoided.

6. Conventional endovascular injection catheters are often manufactured from nitinol memory metal in order to maintain the needle in a nearly full length (about 100 cm) radian and abducted state. However, nickel titanium alloy is softer and the tip is difficult to sharpen, resulting in poor performance in penetrating atherosclerotic plaque and fibrous tissue. Even if the needle is fully extended, it is often difficult to penetrate the vessel wall, making it difficult for the drug to extravasate outside the vessel lumen. In view of the limited volume of the inner wall of the blood vessel, excessive liquid medicine injection is easy to cause hematoma on the inner wall of the blood vessel, split vascular myometrium and even interlayer aneurysm, thereby causing serious complications such as vascular stenosis, obstruction, ischemia and the like.

The invention adopts the medical high-strength 440 steel material which is tougher than nickel-titanium alloy to manufacture the micro-puncture needle, has the advantages of sharp needle tip, tough material, strong penetrating power and the like, is sufficient to penetrate tough lesion areas, can effectively overcome the defects of the material of the existing catheter, and improves the safety and the effectiveness of the injection in the blood vessel cavity. Meanwhile, the guide cone in the puncture needle sheath has a unique structure, and three guide cone holes extending forwards and outwards can accurately guide three micro puncture needles to the outlet and push out. The guide cone design has the advantages that on one hand, the forward thrust is fully utilized to ensure that the puncture needle effectively penetrates through the blood vessel wall, and on the other hand, the tough puncture needle made of common medical steel is possible to avoid using preformed nickel-titanium alloy (the material is softer and the sharpness is insufficient), so that the puncture efficiency is remarkably improved.

7. The side perfusion channel can dynamically monitor the whole injection operation process in real time by means of angiography and synchronously execute therapeutic intervention. The novel intravascular treatment device can continuously inject contrast medium to conduct angiography through the side perfusion channel while carrying out intravascular injection operation by designing the side perfusion channel and the injection conveying pipe which are mutually independent. The innovative design realizes the real-time dynamic monitoring of the blood vessel morphology (including abnormal conditions such as blood vessel interlayer, thrombosis and vasospasm) and provides a reliable basis for the accurate operation in the treatment process and the timely optimization of the treatment scheme. In addition, the device also allows the medical intervention such as medicine injection to be directly carried out through the side perfusion channel, thereby realizing the synchronization of the diagnosis and the treatment in the blood vessel cavity and effectively avoiding the hysteresis diagnosis and the iatrogenic risk possibly caused by the lack of the real-time contrast function of the traditional blood vessel cavity conveying device. Reasonable balance is achieved between efficiency optimization and safety guarantee, and the method is favorable for future clinical transformation and popularization and application.

Drawings

FIG. 1 is a schematic view of a Binlab collapsible microneedle catheter;

FIG. 2 is a schematic illustration of the use of a NIC injection catheter;

FIG. 3 is a schematic diagram of a PEREGRINE infusion catheter system;

FIG. 4 is a schematic view of a microneedle balloon catheter;

FIG. 5 is a view showing the appearance of a flexible endovascular targeted delivery catheter in a contracted state, wherein A is a side view, B is a top view, and C is a bottom view;

FIG. 6 is a cross-sectional view of a flexible endovascular targeted delivery catheter of the invention (the mid-sagittal plane in the contracted state);

FIG. 7 is a cross-sectional view of FIGS. 6a 1-a 8 of the present invention;

FIG. 8 is a cross-sectional view of FIGS. 6 a 9-a 13 in accordance with the present invention;

FIG. 9 is an enlarged view of region D of FIG. 6 in accordance with the present invention;

FIG. 10 is a cross-sectional view of a flexible endovascular targeted delivery catheter of the invention (centered on horizontal plane in the contracted state);

FIG. 11 is an enlarged view of region E of FIG. 10 in accordance with the present invention;

FIG. 12 is a view showing the appearance of a flexible endovascular targeted delivery catheter in a needle-like state, wherein A is a side view, B is a top view, and C is a bottom view;

FIG. 13 is a cross-sectional view of a flexible endovascular targeted delivery catheter of the invention (shown in a needle-like state at mid-horizontal plane);

FIG. 14 is a cross-sectional view of the portion a1 to a8 of FIG. 13 in accordance with the present invention;

FIG. 15 is a cross-sectional view of the portion a9 to a12 of FIG. 13 in accordance with the present invention;

FIG. 16 is an enlarged view of region F of FIG. 13 in accordance with the present invention;

The drawing shows that the guide wire rapid exchange section 1a is an arc-shaped connecting part 2 is a puncture needle sheath 3 is a catheter main body 4 is a puncture needle pushing device 4 is a tube body 5 is an anti-skid pushing button 6 is a pushing sliding block 7 is a conveying tube 8 is a conveying tube outer opening 9 is a guide wire exchange channel outlet 10 is a guide wire exchange channel inlet 11 is a puncture needle outlet 12 is a guide wire exchange channel 13 is a front end metal marking ring 14 is a middle metal marking ring 15 is a rear end metal marking ring 16 is an upper guide rail groove 17 is a lower guide rail groove 18 is a left limiting groove 19 is a right limiting groove 20 is a puncture needle 21 is a puncture needle-conveying tube connecting part 22 is a conveying tube inner cavity 23 is a left guide key 24 is a right guide key 25 is a conveying tube-pushing sliding block connecting part 26 is a middle connecting part 27 is a tail end interface 28 is a micro guide wire, 29 is a side filling tube base 30 is a side filling tube, 31 is a side edge filling tube and a side cone opening 33 is a guide hole.

Detailed Description

In order to make the above features and advantages of the present invention more comprehensible, embodiments accompanied with figures are described in detail below, but the present invention is not limited thereto.

With reference to fig. 5 to 16

A flexible intravascular targeted delivery catheter comprises a guide wire rapid exchange section 1, a puncture needle sheath 2 and a catheter main body 3 which are sequentially connected, wherein the guide wire rapid exchange section 1 is positioned at the front end of the puncture needle sheath 2, a guide wire exchange channel 12 used for passing micro-guide wires 28 is axially arranged in the guide wire rapid exchange section 1, an inlet 10 of the guide wire exchange channel is arranged on one end side wall of the guide wire rapid exchange section 1, which is close to the puncture needle sheath 2, an outlet 9 of the guide wire exchange channel is arranged at the front end of the guide wire rapid exchange section 1, a delivery pipe 7 is arranged in the catheter main body 3, three puncture needles 20 which are uniformly distributed along the circumferential direction and positioned in the puncture needle sheath 2 are connected at the front end of the delivery pipe 7, three puncture needle outlets 11 are uniformly distributed along the circumferential direction on the front side wall of the puncture needle sheath 2, a side perfusion pipe 30 is connected to the rear side wall of the catheter main body 3, a puncture needle pushing device 4 is connected to the rear end of the catheter main body 3, the puncture needle pushing device 4 drives the puncture needle 20 to push out of the puncture needle outlet 11 through the delivery pipe 7, and the puncture needle pushing device 27 is arranged at the rear end of the puncture needle pushing device 4.

In this embodiment, the rear portion of the rapid exchange segment 1 has an arcuate connection portion 1a which is connected to the puncture sheath 2 so that the axis of the wire exchange passage 12 is not on the same axis as the axis of the catheter main body 3. Specifically, the axis of the guidewire exchange channel 12 is parallel to the axis of the catheter body 3, and the axis of the guidewire exchange channel 12 is located on the lower side of the axis of the catheter body 3. The guide wire exchange channel 12 is not parallel to the catheter main body 3, so that the diameter of the catheter main body 3 can be effectively reduced, the guide wire exchange channel is beneficial to being operated to enter into a blood vessel with smaller diameter and a deep tissue, and meanwhile, the manufacturing difficulty is also reduced.

In this embodiment, the front outer wall of the guide wire rapid exchange section 1 is wrapped with a front end metal marking ring 13 which is impermeable to X-rays, so as to facilitate marking and positioning in operation.

In the embodiment, the outer diameter of the guide wire rapid exchange section 1 is 0.7-0.9 mm, the length is 9-11 mm, and the diameter of the guide wire exchange channel is 0.45-0.55 mm. In particular, the guide wire rapid exchange section 1 may have an outer diameter of 0.8mm and a length of 10mm.

In this embodiment, the microcatheter 28 is a 0. inch microcatheter. The guidewire exchange channel 12 is 0.5mm in diameter and instruments can be introduced into the vessel through the 0.018 inch micro-guidewire 28 for precise guiding of the catheter to the target site. In the treatment process, the micro-guide wire 28 can be kept in situ, and once complications such as vasospasm, interlayer, obstruction and the like occur, and auxiliary treatment is needed by other interventional instruments, the micro-guide wire 28 has small caliber and can be well matched with most of treatment instruments, so that the exchange operation is convenient and rapid, and the complications occurring in the treatment process are effectively relieved.

In this embodiment, three puncture needle outlets 11 are uniformly distributed on the front side wall of the puncture needle sheath 2 at 120 ° intervals, so that three micro puncture needles 20 are pushed forward by the rear puncture needle pushing device 4 after reaching the target area position, spread out from the inside of the puncture needle sheath 2 to the front and the outside, puncture or pierce the blood vessel wall, and inject the drug into the delivery tube 7 through the delivery tube outer opening 8 on the tail end interface 27, thereby achieving the purpose of local targeted therapy. When the retraction is in the retraction state, the puncture needle 20 is coated in the puncture needle sheath 2, and enters and exits the blood vessel through the head end guide wire rapid exchange section 1, so that the puncture needle 20 is prevented from protruding out of the catheter to damage the vessel wall.

In this embodiment, the diameter of the puncture needle sheath 2 is 1-1.5 mm, the length is 14-16 mm, and specifically, the length of the puncture needle sheath 2 may be 15mm.

In this embodiment, the puncture needle 20 is a hollow needle, and the puncture needle 20 is prefabricated from medical steel 440 and has an abduction arc shape. When extended from the puncture needle outlet 11, the puncture needle can be deployed forward and outward to puncture the blood vessel wall. The material is harder and sharper than conventional nitinol, and is prone to penetration of plaque such as atherosclerosis and tough fibrous connective tissue.

In this embodiment, three puncture needles 20 are connected to the delivery tube 7 through the puncture needle-delivery tube connection portion 21 in the lumen of the catheter main body 3, and the liquid substance injected through the delivery tube outer port 8 on the tail end interface 27 can be delivered to the target site through the three puncture needles 20.

In this embodiment, a guiding cone 33 is disposed in the puncture needle sheath 2 and near the rear end of the puncture needle outlet 20, three guiding cone holes 34 uniformly distributed along the circumferential direction at 120 ° intervals and used for the three puncture needles 20 to pass through are axially disposed on the guiding cone 33, and the guiding cone holes 34 slightly incline outwards from the rear to the front.

By the three guide tapered holes 34 running forward and outward, the three micropins 20 can be precisely guided to the puncture needle outlet 11 and pushed out. The functional advantages are mainly that firstly, the guiding cone 33 can fully utilize the forward pushing force to ensure that the puncture needle 20 can effectively puncture and penetrate the blood vessel wall, and secondly, the device can enable the puncture needle 20 to be made of common medical steel to be tough enough, so that the use of preformed nickel-titanium alloy materials (which are softer in texture and poor in sharpness) is avoided, and the puncture efficiency is remarkably improved.

In this embodiment, the outer walls of the front and rear ends of the puncture needle sheath 2 are correspondingly wrapped with a middle metal marking ring 14 and a rear metal marking ring 15 which are impermeable to X-rays, so as to distinguish the front guide wire rapid exchange section 1 from the rear catheter main body 3, thereby facilitating positioning calibration in operation.

In this embodiment, a perfusion tube base 29 is fixed to a portion of the left side wall of the rear portion of the catheter main body 3, which is close to the puncture needle pushing device 4, and the side perfusion tube 30 is communicated with the catheter main body 3 through the perfusion tube base 29.

In practice, the design of the lateral perfusion tube 30 has multiple clinical applications. On one hand, the device can be used for injecting normal saline into the catheter through the outer port 31 of the side perfusion tube to empty air in the catheter before operation so as to ensure safe use of the device, and on the other hand, contrast agent can be injected into the target vessel through the outer port 31 of the side perfusion tube during operation to conduct real-time angiography on the target vessel, so that real-time conditions of the vessel can be accurately evaluated, including whether the conditions of interlayer, rupture, spasm or obstruction exist or not. Based on the contrast results, corresponding processing measures can be taken in time. For example, when vasospasm occurs, the spasmolytic can be directly injected through a side perfusion tube, so that rapid and high-efficiency response to complications is realized.

In this embodiment, the length of the catheter body 3 is 1000 to 1200mm, and the diameter is 1 to 1.5mm. The catheter body 3 and the puncture needle sheath 2 have the same caliber.

In this embodiment, the puncture needle pushing device 4 includes a tube body 4a connected to the rear end of the catheter main body 3, a pushing slider 6 is slidably connected to the tube body 4a, an anti-slip push button 5 is provided at the top of the pushing slider 6, and a transverse groove is engraved on the upper surface of the anti-slip push button 5, so that friction force in operation is enhanced, and forward pushing and backward withdrawing operations are facilitated. The pushing slide block 6 is provided with an intermediate connecting part 26 penetrating into the pipe body 4a and fixed with the outer wall of the conveying pipe 7, and the intermediate connecting part 26 is made of high polymer material and is tightly connected with the conveying pipe 7. A matched sliding limiting structure is arranged between the pushing slide block 6 and the outer wall of the pipe body 4 a. The pushing and retracting operations of the puncture needle 20 are performed by the movement of the pushing slider 6.

In this embodiment, the sliding limiting structure includes a left limiting groove 18 and a right limiting groove 19 disposed on the left and right side walls of the pipe body 4a and penetrating in half, and the left and right inner walls of the pushing slider 6 are correspondingly provided with a left guiding key 23 and a right guiding key 24, where the left guiding key 23 and the right guiding key 24 are respectively in mortise-tenon fit with the corresponding left limiting groove 18 and right limiting groove 19. The sliding limit structure matched with the mortise and tenon can realize the sliding limit of the pushing slide block 6, and the pushing and withdrawing operations are convenient to stably carry out.

In this embodiment, the top and bottom of the pipe body 4a are correspondingly provided with an upper guide rail groove 16 and a lower guide rail groove 17, and the intermediate connection portion 26 is fixedly connected with the conveying pipe 7 through the upper guide rail groove 16 and the lower guide rail groove 17.

In this embodiment, the upper guide rail groove 16 and the lower guide rail groove 17 are matched with the left limit groove 18 and the right limit groove 19, so that stability and smoothness of the pushing process can be effectively ensured. In the pushing operation, the guide rail groove provides an accurate guide path for the pushing action, and the limit groove applies an effective limit function to the puncture needle 20 after pushing to the set position, so that the puncture needle is prevented from sliding backward due to external force or improper operation, and the accuracy and reliability of the whole pushing process are ensured.

In this embodiment, the inner center of the intermediate connection portion 26 is tightly connected to the conveying pipe 7 through a conveying pipe-pushing slider connection portion 25 of a high polymer material. The intermediate connection 26 slides back and forth along the upper guide rail groove 16 and the lower guide rail groove 17 of the pusher 4 to push the puncture needle 20 to be deployed and retracted through the puncture needle outlet 11 of the puncture needle sheath 3.

In this embodiment, the surfaces of the left side limit groove 18, the right side limit groove 19, the upper guide rail groove 16 and the lower guide rail groove 17 are provided with graduations with mm as a unit, so that accurate regulation and control of the pushing and withdrawing depth and length of the puncture needle 20 can be realized. Through the quantitative guidance of the scale marks, an operator can accurately adjust the needle insertion depth and the retraction distance of the puncture needle 20 according to specific requirements in the operation process, so that the accuracy and the safety of the operation are ensured, and potential complications caused by improper puncture depth are avoided.

In this embodiment, the diameter of the tube body 4a of the puncture needle pushing device 4 is 4-6mm, and the length is 22-28 mm. Specifically, the tube body 4a of the puncture needle pushing device 4 has a diameter of 5mm and a length of 25mm.

In this embodiment, the pushing slider 6 may have a length of 10 mm and a width of 5 mm.

In this embodiment, the delivery tube 7 extends through the catheter body 3, and the tail end connector 27 of the puncture needle 20 is still exposed at the rear of the puncture needle pushing device 4 in the fully deployed state. The delivery tube 7 is made of medical steel 440, and the outer diameter of the delivery tube is 0.5mm.

In this embodiment, the tail end interface 27 is coated with a polymer material layer, so as to be convenient for connection with an external device such as a syringe.

The design of the single pass delivery tube 7 is different from that of a traditional multi-branch (usually 3-branch) micro-puncture needle catheter. In the conventional design, each puncture needle is provided with an independent delivery tube, and although the structure can realize independent operation of a plurality of puncture needles, the overall hardness of the catheter is inevitably increased, so that the flexibility of the catheter is obviously reduced, and the flexibility of rotation manipulation is limited when the puncture needles pass through tortuous vascular branches. In addition, the high catheter hardness is easy to damage the inner wall of the blood vessel in the pushing process, and serious complications such as blood vessel interlayer and rupture are further caused.

In contrast, the invention effectively reduces the overall hardness of the catheter and further reduces the outer diameter of the catheter by the design of the single-channel delivery tube 7, the front end of which is connected with three puncture needles 20. The design not only optimizes the mechanical property of the catheter and makes the catheter easier to rotate and operate, but also obviously improves the capability of the catheter to pass through the branch of the tiny blood vessel, thereby expanding the application range of the endovascular treatment.

The foregoing is only illustrative of the preferred embodiments of the present invention, and it will be apparent to those skilled in the art from this disclosure that, based upon the teachings herein, no inventive step is required to devise various forms of flexible endovascular targeted delivery catheter, as many changes, modifications, substitutions and variations may be made herein without departing from the spirit and scope of the invention.

Claims (10)

1. A flexible intravascular targeted delivery catheter is characterized by comprising a guide wire rapid exchange section, a puncture needle sheath and a catheter main body which are sequentially connected, wherein the guide wire rapid exchange section is positioned at the front end of the puncture needle sheath, a guide wire exchange channel of a micro guide wire is axially arranged in the guide wire rapid exchange section, an inlet of the guide wire exchange channel is arranged on one end side wall of the guide wire rapid exchange section, which is close to the puncture needle sheath, a delivery pipe is arranged in the catheter main body, three puncture needles which are uniformly distributed along the circumferential direction and are positioned in the puncture needle sheath are connected to the front end of the delivery pipe, three puncture needle outlets are uniformly distributed on the front side wall of the puncture needle sheath along the circumferential direction, a side perfusion pipe is connected to the rear side wall of the catheter main body, a puncture needle pushing device for driving the delivery pipe to push and pull the puncture needle is connected to the rear end of the delivery pipe, and the rear end of the delivery pipe is penetrated by the rear end of the puncture needle pushing device and is provided with a tail end interface.

2. The flexible endovascular targeted delivery catheter according to claim 1, wherein the guidewire rapid exchange segment has an arcuate connection at a rear portion thereof that connects to the introducer sheath such that the axis of the guidewire exchange channel is not co-axial with the axis of the catheter body.

3. The flexible endovascular targeted delivery catheter of claim 1, wherein the three puncture needle outlets are uniformly distributed on the anterior sidewall of the puncture needle sheath at 120 ° intervals from each other, the puncture needles are in an abduction arc shape, and the three puncture needles are connected to the delivery tube within the catheter body lumen by a puncture needle-delivery tube connection.

4. A flexible endovascular targeted delivery catheter according to claim 1 or 3, wherein a guide cone is disposed in the sheath of the spike and near the rear end of the spike outlet, and three guide cone holes are axially disposed on the guide cone, wherein the guide cone holes are uniformly distributed along the circumferential direction and are used for the spike to pass through, and the guide cone holes are inclined outwards from the rear direction to the front direction.

5. The flexible endovascular targeted delivery catheter according to claim 1, wherein the puncture needle pushing device comprises a tube connected to the rear end of the catheter body, a pushing slider is slidably connected to the tube, the pushing slider has an intermediate connection portion penetrating into the tube and fixed to the outer wall of the delivery tube, and a sliding limit structure is disposed between the pushing slider and the outer wall of the tube.

6. The flexible endovascular targeted delivery catheter of claim 5, wherein the sliding limiting structure comprises a left limiting groove and a right limiting groove disposed on a left side wall and a right side wall of the catheter body, and guide keys in mortise and tenon fit with the left limiting groove and the right limiting groove are correspondingly disposed on the left inner wall and the right inner wall of the pushing slide block.

7. The flexible intravascular targeting delivery catheter according to claim 6, wherein the top and bottom of the tube body are correspondingly provided with an upper guide rail groove and a lower guide rail groove, the intermediate connecting portion penetrates through the upper guide rail groove and the lower guide rail groove to be fixedly connected with the delivery tube, and the surfaces of the limiting groove and the guide rail groove are respectively provided with a gradiometer in mm.

8. The flexible endovascular targeted delivery catheter of claim 5, 6 or 7, wherein the intermediate connection is made of a polymeric material and is tightly coupled to the delivery tube, and wherein an anti-slip push button is provided on top of the push slide.

9. The flexible endovascular targeted delivery catheter of claim 1,2, 3,5, 6, or 7, wherein the anterior outer wall of the guidewire rapid exchange segment is wrapped with an X-ray opaque anterior metal marker ring, and the anterior and posterior outer walls of the introducer sheath are correspondingly wrapped with an X-ray opaque central metal marker ring and a posterior metal marker ring.

10. The flexible endovascular targeted delivery catheter of claim 1, 2, 4, 5, 6, or 7, wherein the delivery tube and the spike are both made of medical steel 440, wherein the trailing interface is coated with a layer of polymeric material, wherein a perfusion tube base is secured to a rear sidewall of the catheter body, and wherein the side perfusion tube is in communication with the catheter body via the perfusion tube base.