Novel composite epidural catheter and interlayer combining and fixing mode of catheter

Abstract

The invention provides a novel composite epidural catheter which comprises an inner cavity layer, a magnetic navigation layer, a supporting layer and an antibacterial functional layer, and the inner cavity layer, the magnetic navigation layer, the supporting layer and the antibacterial functional layer are sequentially attached outwards in sequence. All the layers act synergistically to jointly realize magnetic navigation positioning, absorbable degradation and antibacterial functions; wherein an administration channel with a quasi-circular cross section is formed in the inner cavity layer in a surrounding manner, and a conveying channel is provided, so that drugs or anesthetics are continuously or discontinuously injected; the magnetic navigation layer comprises magnetic particles and can realize a real-time navigation function of the tip of the catheter through an external magnetic field; the supporting layer is used for stably supporting the whole novel composite epidural catheter; and the antibacterial function layer provides a daily antibacterial effect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical materials and interventional medical devices, and particularly relates to a novel composite epidural catheter and a catheter interlayer bonding and fixing method. BACKGROUND

[0002] An epidural catheter is an elongated flexible catheter used for epidural anesthesia and postoperative analgesia, usually made of polymer materials such as polyurethane, silicone, etc. The potential gap between the spinal dura and the wall of the spinal canal, the epidural catheter can be placed into the above gap of the epidural space through a puncture needle, and continuously or intermittently infuse local anesthetics or analgesics to block nerve signal conduction, achieve surgical anesthesia or chronic pain management. Clinically, epidural catheters are widely used in cesarean section, lower limb surgery, cancer pain treatment, etc.

[0003] However, the existing epidural catheter is prone to cause inflammation during use due to its long-term retention in the patient's body, greatly reducing the patient's daily comfort. At the same time, the surface of the traditional catheter is prone to bacterial growth and the formation of drug-resistant bacterial biofilm, and long-term retention can increase the incidence of drug-resistant infection in patients. Subsequent treatment of inflammation, infection, etc. caused by catheter retention will increase the risk of secondary trauma, infection and medical costs for patients. In addition, the existing epidural catheter is difficult to position during clinical operation, relying on X-ray (radiation exposure) or ultrasound guidance, especially for patients with spinal deformity, the catheter failure rate is significantly increased.

[0004] It can be seen that how to provide a novel composite epidural catheter and a catheter interlayer bonding and fixing method to improve the positioning efficiency of the epidural catheter during operation, reduce inflammation and infection rate during catheterization, and thus improve the catheter comfort of patients and the treatment efficiency of medical staff is a technical problem that needs to be solved by those skilled in the art. SUMMARY

[0005] In order to solve the above technical problems, in a first aspect, the present application provides a novel composite epidural catheter, the novel composite epidural catheter comprising:

[0006] An inner cavity layer, the inner cavity layer internally surrounding a circular drug delivery channel;

[0007] A magnetic navigation layer, the magnetic navigation layer being disposed on the outer side of the support layer;

[0008] A support layer, the support layer being disposed on the outer side of the magnetic navigation layer;

[0009] An antibacterial functional layer, the antibacterial functional layer being disposed on the outer side of the support layer.

[0010] In the first aspect, the inner cavity layer comprises polyethylene glycol-poly (lactic acid-co-glycolic acid)

[0011] In the first aspect, the wall thickness of the inner cavity layer is 0.1 mm to 0.2 mm.

[0012] In the first aspect, the magnetic navigation layer includes a matrix material and magnetic particles, wherein the magnetic particles are uniformly mixed into the matrix material; wherein the matrix material includes a copolymer of polycaprolactone and polylactic acid-glycolic acid, and the magnetic particles include mesoporous silica-coated iron oxide nanoparticles.

[0013] In the first aspect, the mesoporous silica-coated iron oxide nanoparticles have a particle size of 50 nm to 100 nm; and / or,

[0014] The proportion of mesoporous silica-coated iron oxide nanoparticles is 10-15 wt%.

[0015] In the first aspect, the support layer comprises polylactic acid-glycolic acid copolymer and polycarbonate.

[0016] In the first aspect, the support layer has a mesh-like woven structure.

[0017] In the first aspect, the antibacterial functional layer includes a base layer and an outer coating layer; the base layer uniformly covers the outer side of the support layer, and the outer coating layer is disposed on the outer side of the base layer.

[0018] In the first aspect, the substrate layer comprises mesoporous silica-coated silver nanoparticles and polyurethane; the outer coating comprises pH-responsive antimicrobial peptides and chitosan hydrogel.

[0019] Secondly, the present invention provides a method for interlayer bonding and fixation of a catheter, applied to the aforementioned novel composite epidural catheter. The novel composite epidural catheter includes an inner lumen layer, a magnetic navigation layer, a support layer, and an antibacterial functional layer. The method for interlayer bonding and fixation of the catheter includes:

[0020] The inner cavity layer, the magnetic navigation layer, the support layer, and the antibacterial functional layer are simultaneously heated to a molten state in an inert nitrogen atmosphere, and the temperature is strictly controlled in layers according to the material properties of the inner cavity layer, the magnetic navigation layer, the support layer, and the antibacterial functional layer during the heating process;

[0021] Maleic anhydride-grafted PLGA compatibilizer is added between the magnetic navigation layer and the support layer;

[0022] The inner cavity layer, the magnetic navigation layer, the support layer, and the antibacterial functional layer, which are in a layered temperature-controlled heating and molten state, are formed into the novel composite epidural catheter in one step using a co-extrusion mold;

[0023] After the novel composite hard membrane external conduit is extruded and cooled and solidified, the surface of the novel composite hard membrane external conduit is subjected to low-temperature plasma treatment.

[0024] Beneficial Effects: This invention proposes a novel composite epidural catheter, comprising an inner lumen layer, a magnetic navigation layer, a support layer, and an antibacterial functional layer. These layers are sequentially arranged outwards, working synergistically to achieve magnetic navigation positioning, absorbability and degradation, and antibacterial function. The inner lumen layer forms a near-circular cross-section drug delivery channel, providing a pathway for continuous or intermittent injection of drugs or anesthetics. The magnetic navigation layer includes magnetic particles, enabling real-time navigation of the catheter tip via an external magnetic field. The support layer provides stable support for the entire composite epidural catheter. The antibacterial functional layer provides daily antibacterial protection. Therefore, by providing a novel composite epidural catheter with magnetic navigation, absorbability, and active antibacterial function, this invention improves the accuracy of epidural catheter implantation, reduces complications such as chronic pain or rejection caused by long-term catheter placement due to absorbability, and lowers the infection rate of long-term catheterization through antibacterial function, thereby improving patient comfort and the treatment efficiency of medical staff. Attached Figure Description

[0025] To more clearly illustrate the technical solutions in the embodiments of this specification or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0026] Figure 1 This is a schematic diagram of the structure of the novel composite epidural catheter in Embodiment 1 of the present invention; Attached image description:

[0028] 1. Inner cavity layer; 11. Drug delivery channel; 2. Magnetic navigation layer; 3. Support layer; 4. Antibacterial functional layer; Detailed Implementation

[0029] The technical solutions of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention are within the scope of protection of the present invention.

[0030] Furthermore, in the embodiments of this specification, when a component is referred to as being "fixed to" another component, it can be directly on the other component or there may be an intervening component. When a component is considered to be "connected to" another component, it can be directly connected to the other component or there may be an intervening component. When a component is considered to be "set on" another component, it can be directly set on the other component or there may be an intervening component. The terms "vertical," "horizontal," "left," "right," and similar expressions used in the embodiments of this specification are for illustrative purposes only and are not intended to limit the invention.

[0031] Example 1:

[0032] like Figure 1 As shown, this embodiment provides a novel composite epidural catheter, which includes: an inner lumen layer 1, with a roughly circular drug delivery channel 11 formed inside the inner lumen layer 1; a magnetic navigation layer 2, which is disposed on the outer side of a support layer 3; a support layer 3, which is disposed on the outer side of the magnetic navigation layer 2; and an antibacterial functional layer 4, which is disposed on the outer side of the support layer 3.

[0033] Specifically, Embodiment 1 of the present invention proposes a novel composite epidural catheter. The novel composite epidural catheter includes an inner lumen layer 1, a magnetic navigation layer 2, a support layer 3, and an antibacterial functional layer 4. The inner lumen layer 1, the magnetic navigation layer 2, the support layer 3, and the antibacterial functional layer 4 are sequentially attached outwards, and each layer works synergistically to achieve magnetic navigation positioning, absorbability and degradation, and antibacterial functions. The inner lumen layer 1 has a roughly circular cross-section drug delivery channel 11 inside, providing a delivery channel for continuous or intermittent injection of drugs or anesthetics. The magnetic navigation layer 2 includes magnetic particles, which can achieve real-time navigation of the catheter tip through an external magnetic field. The support layer 3 provides stable support for the entire novel composite epidural catheter. The antibacterial functional layer 4 provides daily antibacterial function.

[0034] In some embodiments, the inner cavity layer 1 comprises polyethylene glycol-polylactic acid-glycolic acid copolymer (PEG-PLGA); wherein the polyethylene glycol (PEG) component can enhance the hydrophilicity of the inner cavity layer 1 and reduce drug adsorption.

[0035] In some embodiments, the wall thickness of the inner cavity layer 1 is 0.1 mm to 0.2 mm.

[0036] In some embodiments, the magnetic navigation layer 2 includes a matrix material and magnetic particles, the magnetic particles being uniformly mixed into the matrix material; wherein, the matrix material includes polycaprolactone (PCL) and polylactic-glycolic acid copolymer (PLGA), which provides high ductility and flexibility, preventing the catheter from breaking when bent, and preventing the navigation layer from collapsing; the magnetic particles include mesoporous silica-coated iron oxide nanoparticles, the mesoporous silica-coated iron oxide (Fe3O4@SiO2) in the magnetic particles being core-shell structured nanoparticles with a SiO2 outer shell and a Fe3O4 core, compared with the metallic magnetic particles (such as pure Fe3O4) used in traditional epidural catheters, by setting a SiO2 outer shell layer, Fe3O4 can be isolated from contact with biological tissues, reducing toxic reactions during drug administration.

[0037] In some embodiments, the particle size of the mesoporous silica-coated iron oxide nanoparticles is 50 nm to 100 nm.

[0038] In some embodiments, the proportion of mesoporous silica-coated iron oxide nanoparticles is 10-15 wt%. The proportion of Fe3O4@SiO2 is 10-15 wt%. Controlling the proportion above 10 wt% ensures sufficient Fe3O4 content, enabling the catheter to generate magnetization force sufficient for clinical navigation even under a 0.1T magnetic field; controlling the proportion below 15 wt% avoids excessive content leading to particle agglomeration and reduced dispersion uniformity.

[0039] In some embodiments, the support layer 3 comprises polylactic acid-glycolic acid copolymer (PLGA) and polycarbonate (PC). Compared to traditional pure PLGA conduits, which are brittle and prone to breakage, this application improves the bending capacity and tensile strength of the support layer 3 by setting it as a composite support layer of polylactic acid-glycolic acid copolymer (PLGA) and polycarbonate (PC), thereby enhancing its support and stability in use.

[0040] In some embodiments, the support layer 3 has a mesh-like woven structure. The mesh-like woven structure can improve the overall resistance to kinking of the conduit and keep the support layer 3 structurally stable and prevent it from collapsing.

[0041] In some embodiments, the antibacterial functional layer 4 includes a base layer and an outer coating layer; the base layer uniformly covers the outer surface of the support layer 3, and the outer coating layer is disposed on the outer surface of the base layer. The base layer uniformly covers the support layer 3, and the outer coating layer uniformly covers and is fixed to the outer surface of the base layer.

[0042] In some embodiments, the substrate layer comprises mesoporous silica-coated silver nanoparticles (Ag@MSNs) and polyurethane (PU); the outer coating comprises a pH-responsive antimicrobial peptide (LL-37) and chitosan hydrogel. The mesoporous silica-coated silver nanoparticles (Ag@MSNs) in the substrate layer continuously release Ag. + Ions inhibit Gram-positive / negative bacteria; the pH-responsive antimicrobial peptide (LL-37) in the outer coating can trigger the release of antimicrobial peptides when the pH at the infection site decreases (pH<6.5), inhibiting drug-resistant bacterial biofilms, reducing the infection rate, and achieving a dual-layer synergistic antimicrobial function.

[0043] Working principle:

[0044] Magnetic navigation and positioning:

[0045] When the novel composite epidural catheter is implanted into the patient's body, an external magnetic field generator produces a gradient magnetic field. The magnetic particles in the magnetic navigation layer 2 at the tip of the epidural catheter are deflected by the magnetic force. The operator can control the path of the epidural catheter by adjusting the direction of the magnetic field outside the body, achieving precise implantation without X-rays and improving surgical efficiency.

[0046] Gradient degradation mechanism:

[0047] Due to the hydrophilicity of the polyethylene glycol (PEG) component, the inner lumen layer 1 can preferentially form micropores 4-6 weeks after epidural catheter implantation, gradually disintegrate, allow tissue ingrowth, and avoid lumen blockage.

[0048] The support layer 3 is a blend of polylactic acid-glycolic acid copolymer and polycarbonate (PLGA-PC). Because polycarbonate (PC) has a certain degree of hydrophobicity, it can delay the degradation of the support layer 3. Therefore, the degradation rate of the support layer 3 is slower than that of the inner lumen layer 1, maintaining the structural integrity during catheter implantation. The support layer 3 can gradually break down 8-12 weeks after epidural catheter implantation and is eventually phagocytosed and metabolized by macrophages. In addition, the support layer 3 has a mesh-like woven structure. Because the mesh pores allow tissue fluid to permeate, it can promote the uniform degradation of the support layer 3 as a whole.

[0049] In this way, by using biodegradable / absorbable materials, chronic pain or rejection caused by long-term epidural catheter retention can be reduced, thereby improving patient comfort and reducing complications.

[0050] Synergistic antibacterial mechanism:

[0051] Daily antibacterial function: The mesoporous silica-coated silver nanoparticles (Ag@MSNs) in the base layer of the antibacterial functional layer 4 can continuously release low doses of silver ions (Ag). + It inhibits the initial adhesion of bacteria and reduces the bacterial adhesion rate on the pipe surface;

[0052] During the infection outbreak phase: When the local pH within the catheter placement area drops below 6.5 due to bacterial metabolism, the chitosan hydrogel in the outer coating of the antibacterial functional layer 4 will protonate and swell, releasing antibacterial peptides, which can react with silver ions (Ag) released from the basal layer. + It can synergistically kill existing drug-resistant bacterial biofilms, thereby achieving the purpose of antibacterial action.

[0053] Example 2:

[0054] This invention provides a method for interlayer bonding and fixation of a catheter, applied to a novel composite epidural catheter as described in Example 1. The novel composite epidural catheter includes an inner lumen layer 1, a magnetic navigation layer 2, a support layer 3, and an antibacterial functional layer 4. The method for interlayer bonding and fixation of the catheter includes:

[0055] The inner cavity layer 1, magnetic navigation layer 2, support layer 3 and antibacterial functional layer 4 are simultaneously heated to a molten state in an inert nitrogen atmosphere, and the temperature is strictly controlled in layers according to the material properties of the inner cavity layer 1, magnetic navigation layer 2, support layer 3 and antibacterial functional layer 4 during the heating process.

[0056] Maleic anhydride-grafted PLGA compatibilizer was added between the magnetic navigation layer 2 and the support layer 3;

[0057] The inner cavity layer 1, magnetic navigation layer 2, support layer 3 and antibacterial functional layer 4, which are in a layered temperature-controlled heating and molten state, are formed into a new type of composite epidural catheter in one step through a co-extrusion mold.

[0058] After the novel composite hard membrane external conduit is extruded and cooled to solidify, the surface of the novel composite hard membrane external conduit is subjected to low-temperature plasma treatment.

[0059] Specifically, during the preparation process, four layers—inner cavity layer 1, magnetic navigation layer 2, support layer 3, and antibacterial functional layer 4—are simultaneously heated to a molten state in an inert nitrogen atmosphere. They are then formed into a composite conduit in a single co-extrusion molding process. The inert nitrogen gas protects the materials, preventing polymer oxidation at high temperatures. Because each layer has a different melting point, the heating process is strictly controlled according to the material properties of each layer to prevent thermal degradation. Furthermore, a maleic anhydride-grafted PLGA compatibilizer is added between the magnetic navigation layer 2 and the support layer 3 to ensure compatibility with both layers. The hydroxyl or carboxyl groups of PCL / PLGA in layer 3 react to form ester bonds (covalent bonds), which enhances the adhesion and bonding strength between the magnetic navigation layer 2 and the support layer 3. In addition, during the preparation of the magnetic navigation layer 2, an electromagnetic forming process is used to orient the magnetic particles along the long axis of the epidural catheter to improve the magnetic response sensitivity. After the novel composite epidural catheter is extruded and cooled and solidified, it is subjected to low-temperature plasma treatment. At this time, the support layer 3 can generate active sites, which form stable covalent bonds with the amino groups (-NH2) on the chitosan hydrogel molecules in the antibacterial functional layer 4, thereby improving the stability and durability of the antibacterial coating 4 and reducing early peeling.

[0060] Finally, it should be noted that the above embodiments are merely specific implementations of the present invention, used to illustrate the technical solutions of the present invention, and not to limit it. The scope of protection of the present invention is not limited thereto. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that any person skilled in the art can still modify or easily conceive of changes to the technical solutions described in the foregoing embodiments within the scope of the technology disclosed in the present invention, or make equivalent substitutions for some of the technical features; and these modifications, changes, or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention. All should be covered within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

[0061] Although embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the specification and embodiments. They can be applied to various fields suitable for the present invention. For those skilled in the art, other modifications can be easily made. Therefore, without departing from the general concept defined by the claims and their equivalents, the present invention is not limited to the specific details and illustrations shown and described herein.

Claims

1. A novel composite epidural catheter, characterized in that, The novel composite epidural catheter includes: An inner cavity layer, wherein a roughly circular drug delivery channel is formed within the inner cavity layer; A magnetic navigation layer is disposed on the outer side of the support layer; A support layer is disposed on the outer surface of the magnetic navigation layer; An antibacterial functional layer is disposed on the outer side of the support layer.

2. The novel composite epidural catheter according to claim 1, characterized in that, The inner cavity layer comprises a polyethylene glycol-polylactic acid-hydroxyacetic acid copolymer.

3. The novel composite epidural catheter according to claim 2, characterized in that, The wall thickness of the inner cavity layer is 0.1mm-0.2mm.

4. The novel composite epidural catheter according to claim 1, characterized in that: The magnetic navigation layer includes a matrix material and magnetic particles, wherein the magnetic particles are uniformly mixed into the matrix material; The matrix material includes a copolymer of polycaprolactone and polylactic acid-glycolic acid, and the magnetic particles include mesoporous silica-coated iron oxide nanoparticles.

5. The novel composite epidural catheter according to claim 4, characterized in that: The mesoporous silica-coated iron oxide nanoparticles have a particle size of 50 nm to 100 nm; and / or, The proportion of mesoporous silica-coated iron oxide nanoparticles is 10-15 wt%.

6. The novel composite epidural catheter according to claim 1, characterized in that, The support layer comprises polylactic acid-glycolic acid copolymer and polycarbonate.

7. The novel composite epidural catheter according to claim 6, characterized in that, The support layer has a mesh-like woven structure.

8. The novel composite epidural catheter according to claim 1, characterized in that, The antibacterial functional layer includes a base layer and an outer coating layer; the base layer is uniformly covered on the outer side of the support layer, and the outer coating layer is disposed on the outer side of the base layer.

9. The novel composite epidural catheter according to claim 8, characterized in that, The base layer comprises mesoporous silica-coated silver nanoparticles and polyurethane; the outer coating comprises pH-responsive antimicrobial peptides and chitosan hydrogel.

10. A method for interlayer bonding and fixation of a catheter, applied to the novel composite epidural catheter as described in any one of claims 1 to 9, wherein the novel composite epidural catheter comprises an inner lumen layer, a magnetic navigation layer, a support layer, and an antibacterial functional layer, characterized in that, The interlayer bonding and fixation methods of the catheter include: The inner cavity layer, the magnetic navigation layer, the support layer, and the antibacterial functional layer are simultaneously heated to a molten state in an inert nitrogen atmosphere, and the temperature is strictly controlled in layers according to the material properties of the inner cavity layer, the magnetic navigation layer, the support layer, and the antibacterial functional layer during the heating process; Maleic anhydride-grafted PLGA compatibilizer is added between the magnetic navigation layer and the support layer; The inner cavity layer, the magnetic navigation layer, the support layer, and the antibacterial functional layer, which are in a layered temperature-controlled heating and molten state, are formed into the novel composite epidural catheter in one step using a co-extrusion mold; After the novel composite hard membrane external conduit is extruded and cooled and solidified, the surface of the novel composite hard membrane external conduit is subjected to low-temperature plasma treatment.

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