Multilayer composite peritoneal dialysis catheter outlet superficial layer infection control medicine patch device

Abstract

The invention relates to a multilayer composite peritoneal dialysis catheter outlet superficial layer infection control medicine patch device, and belongs to the technical field of medical instruments. The device comprises a medicine patch body, a guide rod and a traction strip, the top end of the guide rod is fixedly connected with the right side of the patch body; the upper part of the traction strip is fixedly connected with the lower part of the medicine patch body; according to the device, by optimizing the structural design and material selection, subcutaneous targeted drug delivery, efficient fester adsorption and drainage, non-invasive fixing functions, convenient replacement and other functions can be achieved, and the device is particularly suitable for superficial layer infected parts which are difficult to treat through conventional drug change.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, specifically relating to a multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device. Background Technology

[0002] Peritoneal dialysis is an important treatment for patients with end-stage renal disease. It is a convenient way for patients to undergo renal replacement therapy at home. However, peritoneal dialysis is prone to various complications, such as peritonitis, exit site infection, and tunnel infection. When the condition progresses to a serious level, it can hinder the progress of peritoneal dialysis treatment. Among them, exit site infection (ESI) is a common complication, with an incidence of about 0.1-1.2 times per patient per year. In severe cases, it can lead to peritonitis or catheter removal.

[0003] The peritoneal dialysis catheter exit point refers to the point where, before peritoneal dialysis, a surgical procedure is performed on the patient's abdomen to insert one end of the catheter into the abdominal cavity, while the other end remains outside the abdominal cavity. This is the passageway through which peritoneal dialysis fluid enters and exits the abdominal cavity. The "exit point" refers to the part of the catheter that passes through the abdominal wall and enters the skin from the peritoneal cavity. Managing the catheter exit point is important to ensure proper wound healing, prevent bacterial growth, reduce the chance of infection at the exit point, prevent peritonitis, and extend the lifespan of the peritoneal dialysis catheter.

[0004] The clinical manifestations of exit site infection include purulent discharge at the exit site, with or without skin redness and swelling. The most common pathogens are Staphylococcus aureus and Pseudomonas aeruginosa. Current conventional dressing change methods have the following problems: 1. Limited drug delivery: Superficial subcutaneous infection sites are difficult to cover directly with dressings, leading to insufficient antibiotic penetration. 2. Poor drainage: Ordinary gauze has limited absorbency, cannot effectively remove pus, and easily adheres to newly formed tissue. 3. Complex operation: Traditional drainage devices require repeated implantation, and patients' pain scores (VAS) can typically reach 4-7 points (moderate to severe pain), increasing patient suffering and infection risk. 4. Material defects: Existing dressings have excessively high biocompatibility, easily leading to tissue ingrowth, adhesion, and affecting healing.

[0005] Therefore, overcoming the shortcomings of existing technologies is an urgent problem to be solved in the field of medical device technology. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a multi-layer composite peritoneal dialysis catheter exit superficial infection control patch device. This device is an integrated patch device used to treat superficial purulent infections at the peritoneal dialysis catheter exit site. The device consists of three parts: the patch body, the guide rod, and the traction strip. These three parts achieve integrated therapeutic functions—targeted drug delivery, pus drainage, non-invasive fixation, and convenient replacement—through structural complementarity, material synergy, and functional coupling.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A multi-layer composite peritoneal dialysis catheter exit superficial infection control patch device, including patch body, guide rod, and pull strip; The tip of the guide rod is fixedly connected to the right side of the patch body; The upper part of the pull strip is fixedly connected to the lower part of the patch body; The patch body is a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel; The guide rod is a nickel-titanium alloy guide rod; The tension strip is made of polylactic acid and calcium carbonate composite material.

[0008] Furthermore, the preparation method of the medicated patch body is as follows: Step (1), Preparation of alkaline chitosan solution: Accurately weigh lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water in a mass ratio of 4.4-4.6:6.8-7.2:7.8-8.2:80-81, mix them and stir at room temperature to form a homogeneous mixed solvent; Then, under stirring conditions, chitosan, accounting for 1.4%-1.6% of the total mass of the homogeneous mixed solvent, is slowly added; after the chitosan has been added, stirring continues to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at -29°C to -31°C. After freezing, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution. Step (2), Preparation of alkaline chitosan hydrogel dressing: First, prepare an aqueous solution of 4r-PEG-NH2 with a concentration of 2.9wt%-3.1wt% and an aqueous solution of 4r-PEG-CHO with a concentration of 2.9wt%-3.1wt%. Then, under stirring conditions, 2.9wt%-3.1wt% aqueous solution of 4r-PEG-NH2 and 2.9wt%-3.1wt% aqueous solution of 4r-PEG-CHO were added sequentially to the alkaline chitosan solution prepared in step (1), and then the mixture was stirred to obtain a mixed solution. The ratio of the volume of the alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in 4r-PEG-NH2 with a concentration of 2.9wt%-3.1wt%, and the molar amount of 4r-PEG-CHO in the 4r-PEG-CHO aqueous solution with a concentration of 2.9wt%-3.1wt% is 98mL-102mL: 0.0006mol: 0.0003mol; The mixed solution was then injected into a mold and placed at 64℃-66℃ to react and form a gel. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining an alkaline chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, thereby obtaining a four-armed polyethylene glycol crosslinked chitosan hydrogel, which is the main body of the medicated patch.

[0009] Further, the specific method of step (1) is as follows: Preparation of alkaline chitosan solution: accurately weigh lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water in a mass ratio of 4.5:7:8:80.5, mix them and stir at 300 rpm for 30 minutes at room temperature to form a homogeneous mixed solvent; Subsequently, under continuous stirring at 500 rpm, chitosan, accounting for 1.5% of the total mass of the homogeneous mixed solvent, was added within 60 minutes; after the chitosan was added, stirring was continued at 500 rpm for 1 hour to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at -30°C for 6 hours; then, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution.

[0010] Furthermore, the specific method for step (2) is as follows: First, prepare a 3wt% aqueous solution of 4r-PEG-NH2 and a 3wt% aqueous solution of 4r-PEG-CHO. Then, under stirring at 400 rpm, 3 wt% 4r-PEG-NH2 aqueous solution and 3 wt% 4r-PEG-CHO aqueous solution were added sequentially to the alkaline chitosan solution prepared in step (1), and then the mixture was stirred at 600 rpm for 10 minutes to obtain a mixed solution. The ratio of the volume of the alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in a 3wt% 4r-PEG-NH2 solution, and the molar amount of 4r-PEG-CHO in a 3wt% 4r-PEG-CHO aqueous solution is 100mL: 0.0006mol: 0.0003mol. The mixture was then poured into a mold and placed at 65°C for 30 minutes to form a gel. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining a chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, thereby obtaining a four-armed polyethylene glycol polymer crosslinked chitosan hydrogel, which is the main body of the medicated patch.

[0011] Furthermore, the mold dimensions are 50mm×50mm×2mm; it is repeatedly immersed in deionized water to remove internal alkaline substances. When the pH value of the chitosan hydrogel membrane reaches 7.0±0.3, a four-arm polyethylene glycol polymer crosslinked chitosan hydrogel is obtained.

[0012] Furthermore, the preparation method of the guide rod is as follows: Step A: First, select pure nickel rods and pure titanium rods with a purity higher than 99.99% and weld them into consumable electrodes by plasma arc welding in an argon-protected environment. Step B involves melting and casting the consumable electrode obtained in Step A into an initial ingot using a vacuum consumable solidification furnace. After machining, peeling, and removing the riser, the composition is analyzed to obtain a qualified ingot. Step C: Weld the ingots obtained from multiple steps B into a composite electrode, and put the composite electrode into a vacuum arc remelting furnace for secondary melting. Adjust the melting rate and feeding time to obtain a high-purity ingot with uniform composition. Step D involves heating the high-purity ingot to 850℃±10℃ in a resistance furnace and holding it at that temperature. The ingot is then forged to a Φ30mm rod and its surface is ground. Next, it is precision forged to Φ10mm and then transferred to a critical dimension reduction process to gradually draw the rod to the target diameter. Afterward, it is vacuum annealed at 800-850℃, followed by surface polishing, cutting to the standard length, and medical-grade passivation treatment on the end face. Finally, it is sterilized by gamma irradiation and vacuum-sealed in a cleanroom environment to obtain the guide rod.

[0013] Furthermore, in step A, the welding method involves alternately stacking nickel rods and titanium rods along the length direction to form a four-layer structure of nickel-titanium-nickel-titanium, and sealing the four sides with plasma arc welding to produce a consumable electrode with a cross-section of 40mm×40mm and a length of 300mm. In step B, during vacuum consumable solidification furnace melting, the ultimate vacuum degree is controlled to be ≤5×10⁻⁶. - The melting pressure was 2 Pa, the melting current was 6.5 kA, the voltage was 26 V, and the melting rate was 1.2 kg / min. During casting, the casting temperature was 1580℃±10℃. After standing for 15 seconds, the casting was turned over and poured into a Φ120 mm water-cooled copper mold. The ingot size was Φ120 mm × 300 mm. The analysis of the composition required the following indicators: Ni 55.6-56.4 wt%, O≤0.08 wt%, H≤0.002 wt%, C≤0.05 wt%, Fe≤0.05 wt%, Ti balance, total 100%. In step C, during assembly welding, multiple ingots are coaxially stacked along the axial direction and fixed by electron beam welding, with a vacuum degree ≤5×10⁻⁶. -Vacuum degree ≤ 1×10⁻²Pa, beam current 60mA, welding speed 200mm / min; during secondary melting, vacuum degree ≤ 1×10⁻²Pa, arc stabilizing current 4kA, melting rate 0.8kg / min; when adjusting melting speed and feeding time, the melting rate is maintained at 0.8kg / min, and the current decreases stepwise during the feeding stage: 4kA→2kA→0.5kA, each step for 5min, for a total feeding time of 15min; high purity ingot requirements: Ni 55.6–56.4wt%, O≤0.08wt%, H≤0.002wt%, Ti balance, total 100%; In step D, the high-purity ingot is heated to 850℃±10℃ in a resistance furnace and held for 90 minutes. It is then forged multiple times into a Φ30mm bar using a large-tonnage hydraulic high-speed forging machine, and the surface is ground. Next, it is precision forged to Φ10mm using a rotary forging machine and then transferred to the critical dimension reduction process. The critical dimension reduction process adopts a multi-pass cold drawing process. When the cumulative deformation reaches 40%, it is subjected to intermediate vacuum annealing at 750℃. During this process, powdered graphite lubricant is used to reduce friction loss, and the bar is gradually drawn to the target diameter Φ1.8mm±0.02mm. Then, it is vacuum annealed at 800-850℃, and then the surface is polished to Ra≤0.2μm by a centerless grinder. It is then cut to a standard length of 50±0.1mm by a CNC precision machine tool, and the end face is subjected to medical-grade passivation treatment, requiring a rounding R0.1mm to eliminate sharp edges. Finally, it is sterilized by gamma irradiation and vacuum sealed in a clean room environment to produce a guide rod with a fracture strength >950MPa.

[0014] Furthermore, the multi-pass cold drawing process is as follows: the shrinkage rate per pass is ≤20%, and the specific passes are: Φ10→Φ8.5→Φ7.2→Φ6.1→Φ5.2→Φ4.4→Φ3.7→Φ3.1→Φ2.6→Φ2.2→Φ1.8; During intermediate vacuum annealing, the annealing time is 30 minutes and the vacuum degree is ≤5×10. - ²Pa.

[0015] Furthermore, the preparation method of the tension strip is as follows: S1: Powdered polylactic acid and calcium carbonate powder with a particle size ≤2mm were placed in a drying oven at 79℃-81℃ and dried overnight. The dried polylactic acid particles and calcium carbonate powder were mixed evenly at a mass ratio of 97.8-98.2:2. The mixture was melt-kneaded at 158℃-162℃ under stirring to uniformly disperse calcium carbonate in the polylactic acid matrix, thus obtaining the polylactic acid / calcium carbonate composite PLA-CaCO3. S2: The polylactic acid and calcium carbonate composite PLA-CaCO3 was pulverized and uniformly pressed into PLA-CaCO3 fiber bundles with a thickness of 1.4mm±0.05mm on a flat vulcanizing apparatus. S3: During the preparation of the medicated patch, after the mixed solution is injected into the mold, one end of the PLA-CaCO3 fiber bundle is immediately embedded in the center of the mixed solution, while the other end of the PLA-CaCO3 fiber bundle is exposed outside the mold. Then, it is placed at 64℃-66℃ to react and form a gel, so that the PLA-CaCO3 fiber bundle is combined with the medicated patch.

[0016] Furthermore, the specific method of S1 is as follows: Polylactic acid pulverized to a particle size ≤2mm and calcium carbonate powder with a particle size of 2μm were placed in an 80℃ drying oven and dried overnight. The dried polylactic acid particles and calcium carbonate powder were mixed evenly at a mass ratio of 98:2 and melt-mixed at a temperature of 160℃ and a rotor speed of 80r / min for 12 minutes to uniformly disperse calcium carbonate in the polylactic acid matrix, thus obtaining the polylactic acid / calcium carbonate composite PLA-CaCO3. In S2, the specific method of the pressing process is as follows: keep warm at 160℃ for 10 minutes, pressurize for 6 minutes, pressure is 10MPa, release air 5 times: after each pressurization to 10MPa, immediately release the pressure to 0, with an interval of 30s, and finally vacuum dry at 70℃ to constant weight.

[0017] In this invention, 4r-PEG-NH2 is called a four-armed polyethylene glycol-amino compound; 4r-PEG-CHO is called a four-armed polyethylene glycol-aldehyde compound.

[0018] In this invention, the mixed solution is injected into a mold (50mm×50mm×2mm) and reacted at 65°C for 30 minutes to form a gel. No water needs to be removed during the reaction. The mixture is repeatedly immersed in deionized water to remove internal alkaline substances. When the pH value of the chitosan hydrogel membrane reaches 7.0±0.3, it can be considered that the removal is basically complete, thereby obtaining a four-armed polyethylene glycol polymer crosslinked chitosan hydrogel, which is the main body of the medicated patch.

[0019] Chitosan is a natural alkaline polysaccharide composed of a copolymer of glucosamine and N-acetylglucosamine units linked by β-1,4-glycosidic bonds. It has the following advantages in biomedical applications: (1) its structure is similar to the extracellular matrix; (2) it has excellent biological activity, promoting epithelial cell growth; and (3) it accelerates the repair of different tissues and promotes wound contraction. The positively charged amino groups in chitosan have a strong attraction to the negatively charged bacterial cell walls, which can destroy the bacterial cell walls and thus kill bacteria. In existing technologies, the preparation of chitosan hydrogels often employs traditional acid dissolution methods or cross-linking with small molecule cross-linking agents such as glutaraldehyde. However, the hydrogels prepared by these methods have obvious limitations: acid dissolution causes the amino groups in chitosan molecules to protonate (-NH3). +This weakens its positive charge and antibacterial ability; while using small molecule crosslinking agents may lead to problems such as residual toxicity of the crosslinking agent, high material brittleness, insufficient mechanical strength, and poor water absorption. Unlike existing technologies, one of the core concepts of this invention is the use of a unique alkaline solvent system to dissolve chitosan. The dissolution of chitosan in this alkaline solution is mainly attributed to the solvent disrupting the strong hydrogen bond interactions between and within chitosan molecules, allowing it to disperse rather than based on an acidic dissolution mechanism of protonation. The significant advantage of this method is that it can completely preserve the chemical state of the free amino groups (-NH2) with antibacterial activity on the chitosan molecular chain, thus laying the foundation for the preparation of hydrogels with high antibacterial activity. Another core concept of this invention is the selection of a four-arm polyethylene glycol-aldehyde compound (4r-PEG-CHO) as the main crosslinking agent, which crosslinks with the chitosan molecules dissolved in the above-mentioned alkaline solution through a Schiff base reaction; at the same time, a specific proportion of a four-arm polyethylene glycol-amino compound (4r-PEG-NH2) is introduced as a functional additive. It should be noted that 4r-PEG-CHO itself does not exhibit significant inherent antibacterial activity against common pathogenic bacteria such as Escherichia coli and Staphylococcus aureus. Therefore, if the proportion of 4r-PEG-CHO in the crosslinking system is too high, some amino groups may be consumed due to the Schiff base reaction with the amino groups of chitosan, potentially leading to a decrease in the overall antibacterial ability of the hydrogel. Conversely, this invention has found that the introduction of 4r-PEG-NH2 can significantly improve the antibacterial ability of the prepared hydrogel dressing. This is mainly due to two factors: firstly, the -NH2 groups contained in the 4r-PEG-NH2 molecule itself have certain antibacterial activity; secondly, its introduction helps to form a more flexible crosslinking network structure and may reduce the degree of crosslinking reaction, allowing more antibacterial amino groups on the chitosan chains to be exposed and utilized. Based on the above findings, this invention has successfully prepared a chitosan hydrogel dressing with excellent comprehensive performance by optimizing the formulation. Specifically, in the crosslinking reaction system, the final concentration of 4r-PEG-CHO is 0.003 mol / L and the final concentration of 4r-PEG-NH2 is 0.006 mol / L (i.e., the molar ratio is 1:2).

[0020] The connection between the guide rod and the patch body in this invention is achieved through an interference fit. To this end, a precision assembly channel penetrating the thickness of the patch body is pre-designed and formed during its molding. The diameter of this channel is designed to be slightly smaller than the nominal diameter of the guide rod; for example, for a guide rod with a diameter of Φ1.8mm, the channel diameter can be set to Φ1.7mm ± 0.02mm. During assembly, utilizing the superelasticity of the nickel-titanium alloy and the elastic deformation capability of the hydrogel material, the guide rod is axially pressed into the pre-formed channel of the patch body at room temperature. Relying on the radial elastic clamping force generated by the hydrogel channel wall on the guide rod, and the reverse force generated by the guide rod's own recovery deformation, a strong static friction force is formed at the contact interface, thereby achieving a reliable stress-free connection without the need for external adhesives or mechanical fixation.

[0021] Polylactic acid (PLA), derived from corn and other raw materials, is biodegradable and widely used, but it suffers from poor mechanical properties, low thermal stability, and uncontrollable degradation. Its degradation is influenced by various factors, with the hydrophilicity of the composite playing a crucial role. Calcium carbonate is an environmentally friendly and inexpensive inorganic filler that can improve material stability, hardness, and heat resistance. Composite materials made from calcium carbonate and PLA, compared to pure PLA, not only enhance mechanical properties but also inhibit hydrolysis, making them more suitable for medical and textile fiber applications.

[0022] Preferred materials include polylactic acid with a number-average molecular weight of 135,000, a product of Nature Work LLC, USA; and coated light calcium carbonate with a particle size of 2μm, manufactured by Fuzhou Cangshan Hongbo Additives Factory.

[0023] In this invention, the preferred dimensions of the nickel-titanium alloy guide rod are: Φ1.8mm±0.02mm and length 50mm±0.1mm. The preferred dimensions of the tension strip are: thickness 1.4mm±0.05mm, length 20mm±0.1mm, and width 10mm±0.1mm. The preferred dimensions of the patch body are 50mm×50mm×2mm.

[0024] This invention provides a multi-layer composite peritoneal dialysis catheter exit superficial infection control patch device. This device integrates drug delivery, drainage, and fixation functions, and, combined with special materials and structural design, significantly improves the infection control effect.

[0025] This invention adopts an integrated structure, and its design principle is as follows: (1) The main body of the patch: As the functional core of the device, it adopts a four-arm polyethylene glycol (4r-PEG) high molecular cross-linked chitosan hydrogel, which has antibacterial, liquid absorption and bioadhesion functions. The patch is wrapped around the guide rod, and the edge of the patch is embedded with a traction strip to achieve non-invasive fixation and mechanical cushioning.

[0026] (2) Guide rod: As the mechanical support and implantation guide unit of the device, it is made of super-elastic nickel-titanium alloy. The front end is passivated to avoid tissue damage, and the rear end forms an interference fit with the channel of the medicated patch body (diameter difference ≤ 0.1 mm) to ensure that the medicated patch body is delivered to the infected site synchronously during implantation.

[0027] (3) Traction strip: As the external fixation and mechanical adjustment unit of the device, it is made of polylactic acid (PLA) / calcium carbonate composite fiber. One end is embedded in the edge of the patch body through covalent cross-linking (Schiff base bond) + physical entanglement, and the other end is reserved for external part (2cm) for tensionless fixation and progressive traction (adjustment range ≤2mm / time).

[0028] Compared with the prior art, the beneficial effects of this invention are as follows: (1) Targeted drug delivery: When the guide rod is implanted, the subcutaneous tunnel is opened by superelastic deformation, so that the patch body is closely attached to the infection site. The amino groups of the four-arm polyethylene glycol polymer cross-linked chitosan hydrogel are electrostatically bound to the bacterial cell wall, thereby increasing the local drug concentration by 3 times (MIC is reduced to 100mg / 10mL).

[0029] (2) High efficiency drainage: The three-dimensional network structure of the four-arm polyethylene glycol polymer cross-linked chitosan hydrogel expands in volume after adsorbing pus. The mechanical rebound of the traction strip can produce periodic micro-deformation (frequency 0.5Hz), which promotes the migration of pus into the gel. The drainage efficiency is 5 times higher than that of traditional gauze.

[0030] (3) Non-invasive fixation: The super elasticity of the nickel-titanium alloy guide rod can buffer external force impact (deformation recovery rate ≥98%), and the PLA-based fiber of the traction strip softens at body temperature (glass transition temperature 55℃), avoiding skin cuts caused by traction, and reducing the pain score (VAS) to ≤2 points.

[0031] (4) Convenient replacement: Simplified implantation and replacement (operation time < 5 minutes), avoiding surgical intervention (when the depth of infection is ≤ 5 mm).

[0032] (5) Safe and durable: The biocompatibility of the material reduces the risk of allergies and adhesions; the device has a shelf life of 24 months and is suitable for home dialysis scenarios.

[0033] The device of this invention, through optimized structural design and material selection, can achieve functions such as subcutaneous targeted drug delivery, efficient pus absorption and drainage, non-invasive fixation, and convenient replacement, and is especially suitable for superficial infection sites that are difficult to treat with conventional dressing changes. Attached Figure Description

[0034] Figure 1 This is a front view of the multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device of the present invention; wherein, 1 is the patch body, 2 is the guide rod, and 3 is the pull strip; Figure 2 This is an unfolded view of the multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device of the present invention; wherein, 1 is the patch body, 2 is the guide rod, and 3 is the traction strip; Figure 3 This is a cross-sectional view of the connection between the guide rod and the patch body of the multilayer composite peritoneal dialysis catheter outlet superficial infection control patch device of the present invention; wherein, 1 is the patch body and 2 is the guide rod; Figure 4 This is a schematic diagram of the inhibition zone for testing the antibacterial performance of the multilayer composite peritoneal dialysis catheter outlet superficial infection control patch device of the present invention; wherein, (a) is the acidic chitosan hydrogel group; (b) is the alkaline chitosan hydrogel group; (c) is the 4r-PEG-CHO variable group; and (d) is the 4r-PEG-NH2 variable group. Figure 5 The images show fluorescence images of dead-to-live Escherichia coli in the multilayer composite peritoneal dialysis catheter outlet superficial infection control patch device of the present invention; (a) is the fluorescence image of the control group after 6 hours of culture; (b) is the fluorescence image of the control group after 12 hours of culture; (c) is the fluorescence image of the four-arm polyethylene glycol cross-linked chitosan hydrogel treatment group after 6 hours of culture; and (d) is the fluorescence image of the four-arm polyethylene glycol cross-linked chitosan hydrogel treatment group after 12 hours of culture. Figure 6 This image shows the OD value detection results of Staphylococcus aureus in the control and experimental groups of the multilayer composite peritoneal dialysis catheter outlet superficial infection control patch device of the present invention. Figure 7 The figure shows the minimum inhibitory concentration (MIC) test results of the superficial infection control patch device for the multilayer composite peritoneal dialysis catheter outlet of the present invention; where X represents the concentration of the four-arm polyethylene glycol cross-linked chitosan hydrogel at X mg / 10 mL; (a) shows the effect of the four-arm polyethylene glycol cross-linked chitosan hydrogel concentration at 0 mg / 10 mL (control group) on the colony growth of Staphylococcus aureus; (b) shows the effect of the four-arm polyethylene glycol cross-linked chitosan hydrogel concentration at 20 mg / 10 mL on the colony growth of Staphylococcus aureus; (c) shows the effect of the four-arm polyethylene glycol cross-linked chitosan hydrogel concentration at 20 mg / 10 mL on the colony growth of Staphylococcus aureus. The effects of the concentration of cross-linked polyethylene glycol (CPEG) chitosan hydrogel at 40 mg / 10 mL on the colony growth of Staphylococcus aureus; (d) the effects of the concentration of four-armed CPEG chitosan hydrogel at 60 mg / 10 mL on the colony growth of Staphylococcus aureus; (e) the effects of the concentration of four-armed CPEG chitosan hydrogel at 80 mg / 10 mL on the colony growth of Staphylococcus aureus; and (f) the effects of the concentration of four-armed CPEG chitosan hydrogel at 100 mg / 10 mL on the colony growth of Staphylococcus aureus. Figure 8The images are fluorescence micrographs of the cytotoxicity test of the multilayer composite peritoneal dialysis catheter outlet superficial infection control patch device of the present invention; wherein, (a) is the fluorescence image of the experimental group after 24 hours of culture; (b) is the fluorescence image of the experimental group after 72 hours of culture; and (c) is the fluorescence image of the experimental group after 120 hours of culture. Figure 9 This is a quantitative analysis chart of the percentage of viable cell growth rate of the multilayer composite peritoneal dialysis catheter outlet superficial infection control patch device of the present invention; Figure 10 The figure shows the effect of calcium carbonate content on the mechanical properties of PLA-CaCO3 composite material; where (a) is the change of tensile strength with CaCO3 content (0%-7%); (b) is the change of elongation at break with CaCO3 content; (c) is the change of elastic modulus with CaCO3 content; and (d) is the change of maximum load with CaCO3 content. Detailed Implementation

[0035] The present invention will now be described in further detail with reference to the embodiments.

[0036] Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be construed as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed in accordance with the techniques or conditions described in the literature in the field or according to the product instructions. Materials or equipment whose manufacturers are not specified are all conventional products that can be obtained by purchase.

[0037] Example 1 like Figures 1-3 As shown, the multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device includes a patch body, a guide rod, and a pull strip; The tip of the guide rod is fixedly connected to the right side of the patch body; The upper part of the pull strip is fixedly connected to the lower part of the patch body; The patch body is a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel; The guide rod is a nickel-titanium alloy guide rod; The tension strip is made of polylactic acid and calcium carbonate composite material.

[0038] Example 2 like Figures 1-3 As shown, the multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device includes a patch body, a guide rod, and a pull strip; The tip of the guide rod is fixedly connected to the right side of the patch body; The upper part of the pull strip is fixedly connected to the lower part of the patch body; The patch body is a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel; The guide rod is a nickel-titanium alloy guide rod; The tension strip is made of polylactic acid and calcium carbonate composite material.

[0039] The preparation method of the medicated patch body is as follows: Step (1), Preparation of alkaline chitosan solution: Lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water are accurately weighed in a mass ratio of 4.4:6.8:7.8:80, mixed and stirred at room temperature to form a homogeneous mixed solvent; Then, under stirring conditions, chitosan, accounting for 1.4% of the total mass of the homogeneous mixed solvent, is slowly added; after the chitosan has been added, stirring is continued to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at −29°C; after freezing, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution. Step (2), Preparation of alkaline chitosan hydrogel dressing: First, prepare an aqueous solution of 4r-PEG-NH2 with a concentration of 2.9 wt% and an aqueous solution of 4r-PEG-CHO with a concentration of 2.9 wt%. Then, under stirring conditions, 2.9 wt% 4r-PEG-NH2 aqueous solution and 2.9 wt% 4r-PEG-CHO aqueous solution were added sequentially to the alkaline chitosan solution obtained in step (1), and then the mixture was stirred to obtain a mixed solution. The ratio of the volume of the alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in a 2.9wt% 4r-PEG-NH2 solution, and the molar amount of 4r-PEG-CHO in a 2.9wt% 4r-PEG-CHO aqueous solution is 98 mL: 0.0006 mol: 0.0003 mol. The mixed solution was then injected into a mold and placed at 64°C to react and form a gel. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining an alkaline chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, thereby obtaining a four-armed polyethylene glycol crosslinked chitosan hydrogel, which is the main body of the medicated patch.

[0040] The preparation method of the guide rod is as follows: Step A: First, select pure nickel rods and pure titanium rods with a purity higher than 99.99% and weld them into consumable electrodes by plasma arc welding in an argon-protected environment. Step B involves melting and casting the consumable electrode obtained in Step A into an initial ingot using a vacuum consumable solidification furnace. After machining, peeling, and removing the riser, the composition is analyzed to obtain a qualified ingot. Step C: Weld the ingots obtained from multiple steps B into a composite electrode, and put the composite electrode into a vacuum arc remelting furnace for secondary melting. Adjust the melting rate and feeding time to obtain a high-purity ingot with uniform composition. Step D involves heating the high-purity ingot to 850℃±10℃ in a resistance furnace and holding it at that temperature. The ingot is then forged to a Φ30mm rod and its surface is ground. Next, it is precision forged to Φ10mm and then transferred to a critical dimension reduction process to gradually draw the rod to the target diameter. Afterward, it is vacuum annealed at 800-850℃, followed by surface polishing, cutting to the standard length, and medical-grade passivation treatment on the end face. Finally, it is sterilized by gamma irradiation and vacuum-sealed in a cleanroom environment to obtain the guide rod.

[0041] The preparation method of the tension strip is as follows: S1: Powdered polylactic acid and calcium carbonate powder with a particle size ≤2mm were placed in a drying oven at 79℃ and dried overnight. The dried polylactic acid particles and calcium carbonate powder were mixed evenly at a mass ratio of 97.8:2. The mixture was melt-kneaded at 158℃ under stirring to make calcium carbonate evenly dispersed in the polylactic acid matrix, thus obtaining the polylactic acid / calcium carbonate composite PLA-CaCO3. S2: The polylactic acid and calcium carbonate composite PLA-CaCO3 was pulverized and uniformly pressed into PLA-CaCO3 fiber bundles with a thickness of 1.4mm±0.05mm on a flat vulcanizing apparatus. S3: During the preparation of the medicated patch, after the mixed solution is injected into the mold, one end of the PLA-CaCO3 fiber bundle is immediately embedded in the center of the mixed solution, while the other end of the PLA-CaCO3 fiber bundle is exposed outside the mold. Then, it is placed at 64°C to react and form a gel, so that the PLA-CaCO3 fiber bundle is combined with the medicated patch.

[0042] Example 3 like Figures 1-3 As shown, the multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device includes a patch body, a guide rod, and a pull strip; The tip of the guide rod is fixedly connected to the right side of the patch body; The upper part of the pull strip is fixedly connected to the lower part of the patch body; The patch body is a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel; The guide rod is a nickel-titanium alloy guide rod; The tension strip is made of polylactic acid and calcium carbonate composite material.

[0043] The preparation method of the medicated patch body is as follows: Step (1), Preparation of alkaline chitosan solution: Accurately weigh lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water in a mass ratio of 4.6:7.2:8.2:81, mix them and stir at room temperature to form a homogeneous mixed solvent; Then, under stirring conditions, chitosan, accounting for 1.6% of the total mass of the homogeneous mixed solvent, is slowly added; after the chitosan has been added, stirring is continued to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at -31°C; after freezing, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution. Step (2), Preparation of alkaline chitosan hydrogel dressing: First, prepare an aqueous solution of 4r-PEG-NH2 with a concentration of 2.9wt%-3.1wt% and an aqueous solution of 4r-PEG-CHO with a concentration of 3.1wt%. Then, under stirring conditions, 3.1 wt% 4r-PEG-NH2 aqueous solution and 3.1 wt% 4r-PEG-CHO aqueous solution were added sequentially to the alkaline chitosan solution prepared in step (1), and then the mixture was stirred to obtain a mixed solution. The ratio of the volume of the alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in a 3.1wt% 4r-PEG-NH2 solution, and the molar amount of 4r-PEG-CHO in a 3.1wt% 4r-PEG-CHO aqueous solution is 102 mL: 0.0006 mol: 0.0003 mol. The mixed solution was then injected into a mold and placed at 66°C to react and form a gel. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining an alkaline chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, thereby obtaining a four-armed polyethylene glycol crosslinked chitosan hydrogel, which is the main body of the medicated patch.

[0044] The preparation method of the guide rod is as follows: Step A: First, select pure nickel rods and pure titanium rods with a purity higher than 99.99% and weld them into consumable electrodes by plasma arc welding in an argon-protected environment. Step B involves melting and casting the consumable electrode obtained in Step A into an initial ingot using a vacuum consumable solidification furnace. After machining, peeling, and removing the riser, the composition is analyzed to obtain a qualified ingot. Step C: Weld the ingots obtained from multiple steps B into a composite electrode, and put the composite electrode into a vacuum arc remelting furnace for secondary melting. Adjust the melting rate and feeding time to obtain a high-purity ingot with uniform composition. Step D involves heating the high-purity ingot to 850℃±10℃ in a resistance furnace and holding it at that temperature. The ingot is then forged to a Φ30mm rod and its surface is ground. Next, it is precision forged to Φ10mm and then transferred to a critical dimension reduction process to gradually draw the rod to the target diameter. Afterward, it is vacuum annealed at 800-850℃, followed by surface polishing, cutting to the standard length, and medical-grade passivation treatment on the end face. Finally, it is sterilized by gamma irradiation and vacuum-sealed in a cleanroom environment to obtain the guide rod.

[0045] The preparation method of the tension strip is as follows: S1: Powdered polylactic acid and calcium carbonate powder with a particle size ≤2mm were placed in an 81℃ drying oven and dried overnight. The dried polylactic acid particles and calcium carbonate powder were mixed evenly at a mass ratio of 98.2:2. The mixture was melt-kneaded at 162℃ under stirring to make calcium carbonate uniformly dispersed in the polylactic acid matrix, thus obtaining the polylactic acid / calcium carbonate composite PLA-CaCO3. S2: The polylactic acid and calcium carbonate composite PLA-CaCO3 was pulverized and uniformly pressed into PLA-CaCO3 fiber bundles with a thickness of 1.4mm±0.05mm on a flat vulcanizing apparatus. S3: During the preparation of the medicated patch, after the mixed solution is injected into the mold, one end of the PLA-CaCO3 fiber bundle is immediately embedded in the center of the mixed solution, while the other end of the PLA-CaCO3 fiber bundle is exposed outside the mold. Then, it is placed at 66°C to react and form a gel, so that the PLA-CaCO3 fiber bundle is combined with the medicated patch.

[0046] Example 4 like Figures 1-3 As shown, the multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device includes a patch body, a guide rod, and a pull strip; The tip of the guide rod is fixedly connected to the right side of the patch body; The upper part of the pull strip is fixedly connected to the lower part of the patch body; The patch body is a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel; The guide rod is a nickel-titanium alloy guide rod; The tension strip is made of polylactic acid and calcium carbonate composite material.

[0047] The preparation method of the medicated patch body is as follows: Step (1), Preparation of alkaline chitosan solution: Accurately weigh lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water in a mass ratio of 4.5:7:8:80.5, mix them and stir at room temperature to form a homogeneous mixed solvent; Then, under stirring conditions, chitosan, accounting for 1.5% of the total mass of the homogeneous mixed solvent, is slowly added; after the chitosan has been added, stirring is continued to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at -30°C; after freezing, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution. Step (2), Preparation of alkaline chitosan hydrogel dressing: First, prepare a 3wt% aqueous solution of 4r-PEG-NH2 and a 3wt% aqueous solution of 4r-PEG-CHO. Then, under stirring conditions, 3wt% 4r-PEG-NH2 aqueous solution and 3wt% 4r-PEG-CHO aqueous solution were added sequentially to the alkaline chitosan solution obtained in step (1), and then the mixture was stirred to obtain a mixed solution. The ratio of the volume of the alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in a 3wt% 4r-PEG-NH2 solution, and the molar amount of 4r-PEG-CHO in a 3wt% 4r-PEG-CHO aqueous solution is 100mL: 0.0006mol: 0.0003mol. The mixed solution was then injected into a mold and placed at 65°C to react and form a gel. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining an alkaline chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, thereby obtaining a four-armed polyethylene glycol crosslinked chitosan hydrogel, which is the main body of the medicated patch.

[0048] The preparation method of the guide rod is as follows: Step A: First, select pure nickel rods and pure titanium rods with a purity higher than 99.99% and weld them into consumable electrodes by plasma arc welding in an argon-protected environment. Step B involves melting and casting the consumable electrode obtained in Step A into an initial ingot using a vacuum consumable solidification furnace. After machining, peeling, and removing the riser, the composition is analyzed to obtain a qualified ingot. Step C: Weld the ingots obtained from multiple steps B into a composite electrode, and put the composite electrode into a vacuum arc remelting furnace for secondary melting. Adjust the melting rate and feeding time to obtain a high-purity ingot with uniform composition. Step D involves heating the high-purity ingot to 850℃±10℃ in a resistance furnace and holding it at that temperature. The ingot is then forged to a Φ30mm rod and its surface is ground. Next, it is precision forged to Φ10mm and then transferred to a critical dimension reduction process to gradually draw the rod to the target diameter. Afterward, it is vacuum annealed at 800-850℃, followed by surface polishing, cutting to the standard length, and medical-grade passivation treatment on the end face. Finally, it is sterilized by gamma irradiation and vacuum-sealed in a cleanroom environment to obtain the guide rod.

[0049] The preparation method of the tension strip is as follows: S1: Place polylactic acid and calcium carbonate powder, which are pulverized to a particle size ≤2mm, into an 80℃ drying oven and dry overnight. Mix the dried polylactic acid particles and calcium carbonate powder at a mass ratio of 98:2. Melt and knead the mixture at 159℃ under stirring to make calcium carbonate uniformly dispersed in the polylactic acid matrix, thus obtaining the polylactic acid / calcium carbonate composite PLA-CaCO3. S2: The polylactic acid and calcium carbonate composite PLA-CaCO3 was pulverized and uniformly pressed into PLA-CaCO3 fiber bundles with a thickness of 1.4mm±0.05mm on a flat vulcanizing apparatus. S3: During the preparation of the medicated patch, after the mixed solution is injected into the mold, one end of the PLA-CaCO3 fiber bundle is immediately embedded in the center of the mixed solution, while the other end of the PLA-CaCO3 fiber bundle is left exposed outside the mold. Then, it is placed at 65°C to react and form a gel, so that the PLA-CaCO3 fiber bundle is combined with the medicated patch.

[0050] Example 5 like Figures 1-3 As shown, the multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device includes a patch body, a guide rod, and a pull strip; The tip of the guide rod is fixedly connected to the right side of the patch body; The upper part of the pull strip is fixedly connected to the lower part of the patch body; The patch body is a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel; The guide rod is a nickel-titanium alloy guide rod; The tension strip is made of polylactic acid and calcium carbonate composite material.

[0051] The preparation method of the medicated patch body is as follows: Step (1), Preparation of alkaline chitosan solution: Lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water were accurately weighed in a mass ratio of 4.5:7:8:80.5. After mixing, the mixture was stirred at 300 rpm for 30 minutes at room temperature to form a homogeneous mixed solvent. Then, under continuous stirring at 500 rpm, chitosan accounting for 1.5% of the total mass of the homogeneous mixed solvent was added within 60 minutes; after the chitosan was added, stirring was continued at 500 rpm for 1 hour to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at -30°C for 6 hours; then, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution.

[0052] Step (2), Preparation of alkaline chitosan hydrogel dressing: Preparation of alkaline chitosan hydrogel dressing: First, prepare a 3wt% aqueous solution of 4r-PEG-NH2 and a 3wt% aqueous solution of 4r-PEG-CHO. Then, under stirring at 400 rpm, 3 wt% 4r-PEG-NH2 aqueous solution and 3 wt% 4r-PEG-CHO aqueous solution were added sequentially to the alkaline chitosan solution prepared in step (1), and then the mixture was stirred at 600 rpm for 10 minutes to obtain a mixed solution. The ratio of the volume of the alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in a 3wt% 4r-PEG-NH2 solution, and the molar amount of 4r-PEG-CHO in a 3wt% 4r-PEG-CHO aqueous solution is 100mL: 0.0006mol: 0.0003mol. The mixture was then poured into a mold and placed at 65°C for 30 minutes to form a gel. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining a chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, thereby obtaining a four-arm polyethylene glycol crosslinked chitosan hydrogel, which is the main body of the medicated patch.

[0053] The mold dimensions are 50mm×50mm×2mm; it is repeatedly immersed in deionized water to remove internal alkaline substances. When the pH value of the chitosan hydrogel membrane reaches 7.0±0.3, a four-arm polyethylene glycol crosslinked chitosan hydrogel is obtained.

[0054] The preparation method of the guide rod is as follows: Step A: First, select pure nickel rods and pure titanium rods with a purity higher than 99.99% and weld them into consumable electrodes by plasma arc welding in an argon-protected environment. Step B involves melting and casting the consumable electrode obtained in Step A into an initial ingot using a vacuum consumable solidification furnace. After machining, peeling, and removing the riser, the composition is analyzed to obtain a qualified ingot. Step C: Weld the ingots obtained from multiple steps B into a composite electrode, and put the composite electrode into a vacuum arc remelting furnace for secondary melting. Adjust the melting rate and feeding time to obtain a high-purity ingot with uniform composition. Step D involves heating the high-purity ingot to 850℃±10℃ in a resistance furnace and holding it at that temperature. The ingot is then forged to a Φ30mm rod and its surface is ground. Next, it is precision forged to Φ10mm and then transferred to a critical dimension reduction process to gradually draw the rod to the target diameter. Afterward, it is vacuum annealed at 800-850℃, followed by surface polishing, cutting to the standard length, and medical-grade passivation treatment on the end face. Finally, it is sterilized by gamma irradiation and vacuum-sealed in a cleanroom environment to obtain the guide rod.

[0055] In step A, the assembly welding method is to alternately stack nickel rods and titanium rods along the length direction to form a four-layer structure of nickel-titanium-nickel-titanium, and then seal the four sides with plasma arc welding to make a consumable electrode with a cross-section of 40mm×40mm and a length of 300mm. In step B, during vacuum consumable solidification furnace melting, the ultimate vacuum degree is controlled to be ≤5×10⁻⁶. - The melting pressure was 2 Pa, the melting current was 6.5 kA, the voltage was 26 V, and the melting rate was 1.2 kg / min. During casting, the casting temperature was 1580℃±10℃. After standing for 15 seconds, the casting was turned over and poured into a Φ120 mm water-cooled copper mold. The ingot size was Φ120 mm × 300 mm. The analysis of the composition required the following indicators: Ni 55.6-56.4 wt%, O≤0.08 wt%, H≤0.002 wt%, C≤0.05 wt%, Fe≤0.05 wt%, Ti balance, total 100%. In step C, during assembly welding, multiple ingots are coaxially stacked along the axial direction and fixed by electron beam welding, with a vacuum degree ≤5×10⁻⁶. - Vacuum degree ≤ 1×10⁻²Pa, beam current 60mA, welding speed 200mm / min; during secondary melting, vacuum degree ≤ 1×10⁻²Pa, arc stabilizing current 4kA, melting rate 0.8kg / min; when adjusting melting speed and feeding time, the melting rate is maintained at 0.8kg / min, and the current decreases stepwise during the feeding stage: 4kA→2kA→0.5kA, each step for 5min, for a total feeding time of 15min; high purity ingot requirements: Ni 55.6–56.4wt%, O≤0.08wt%, H≤0.002wt%, Ti balance, total 100%; In step D, the high-purity ingot is heated to 850℃±10℃ in a resistance furnace and held for 90 minutes. It is then forged multiple times into a Φ30mm bar using a large-tonnage hydraulic high-speed forging machine, and the surface is ground. Next, it is precision forged to Φ10mm using a rotary forging machine and then transferred to the critical dimension reduction process. The critical dimension reduction process adopts a multi-pass cold drawing process. When the cumulative deformation reaches 40%, it is subjected to intermediate vacuum annealing at 750℃. During this process, powdered graphite lubricant is used to reduce friction loss, and the bar is gradually drawn to the target diameter Φ1.8mm±0.02mm. Then, it is vacuum annealed at 800-850℃, and then the surface is polished to Ra≤0.2μm by a centerless grinder. It is then cut to a standard length of 50±0.1mm by a CNC precision machine tool, and the end face is subjected to medical-grade passivation treatment, requiring a rounding R0.1mm to eliminate sharp edges. Finally, it is sterilized by gamma irradiation and vacuum sealed in a clean room environment to produce a guide rod with a fracture strength >950MPa.

[0056] The multi-pass cold drawing process is as follows: the shrinkage rate of each pass is ≤20%, and the specific passes are: Φ10→Φ8.5→Φ7.2→Φ6.1→Φ5.2→Φ4.4→Φ3.7→Φ3.1→Φ2.6→Φ2.2→Φ1.8; During intermediate vacuum annealing, the annealing time is 30 minutes and the vacuum degree is ≤5×10. - ²Pa.

[0057] The preparation method of the tension strip is as follows: S1: Polylactic acid pulverized to a particle size ≤2mm and calcium carbonate powder with a particle size of 2μm were placed in an 80℃ drying oven and dried overnight. The dried polylactic acid particles and calcium carbonate powder were mixed evenly at a mass ratio of 98:2. The mixture was melt-kneaded at a temperature of 160℃ and a rotor speed of 80r / min for 12 minutes to uniformly disperse calcium carbonate in the polylactic acid matrix, thus obtaining the polylactic acid / calcium carbonate composite PLA-CaCO3. S2: The polylactic acid and calcium carbonate composite PLA-CaCO3 was pulverized and uniformly pressed into PLA-CaCO3 fiber bundles with a thickness of 1.4mm±0.05mm on a flat vulcanizing apparatus. The specific method of the pressing process is as follows: keep warm at 160℃ for 10 minutes, pressurize for 6 minutes, pressure is 10MPa, release air 5 times: after each pressurization to 10MPa, immediately release the pressure to 0, with an interval of 30s, and finally vacuum dry at 70℃ to constant weight.

[0058] S3: During the preparation of the medicated patch, after the mixed solution is injected into the mold, one end of the PLA-CaCO3 fiber bundle is immediately embedded in the center of the mixed solution, while the other end of the PLA-CaCO3 fiber bundle is left exposed outside the mold. Then, it is placed at 65°C to react and form a gel, so that the PLA-CaCO3 fiber bundle is combined with the medicated patch.

[0059] Example 6 like Figures 1-3 As shown, the multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device includes a patch body, a guide rod, and a pull strip; The tip of the guide rod is fixedly connected to the right side of the patch body; The upper part of the pull strip is fixedly connected to the lower part of the patch body; The patch body is a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel; The guide rod is a nickel-titanium alloy guide rod; The tension strip is made of polylactic acid and calcium carbonate composite material.

[0060] The preparation method of the medicated patch body includes the following steps: Step (1), Preparation of alkaline chitosan solution: Accurately weigh lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water in a mass ratio of 4.5:7:8:80.5, mix them and stir at 300 rpm for 30 minutes at room temperature to form a homogeneous mixed solvent; Then, under continuous stirring at 500 rpm, chitosan accounting for 1.5% of the total mass of the homogeneous mixed solvent was added within 60 minutes; after the chitosan was added, stirring was continued at 500 rpm for 1 hour to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at -30°C for 6 hours; then, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution.

[0061] Step (2), Preparation of alkaline chitosan hydrogel dressing: First, prepare an aqueous solution of 4r-PEG-NH2 (a tetra-armed polyethylene glycol-amino compound) with a concentration of 3wt% and an aqueous solution of 4r-PEG-CHO (a tetra-armed polyethylene glycol-aldehyde compound) with a concentration of 3wt%. Then, under stirring at 400 rpm, 3 wt% 4r-PEG-NH2 aqueous solution and 3 wt% 4r-PEG-CHO aqueous solution were added sequentially to the alkaline chitosan solution prepared in step (1), and then the mixture was stirred at 600 rpm for 10 minutes to obtain a mixed solution. The ratio of the volume of a 1.5% alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in a 3wt% 4r-PEG-NH2 solution, and the molar amount of 4r-PEG-CHO in a 3wt% 4r-PEG-CHO aqueous solution is 100mL:0.0006mol:0.0003mol. The mixed solution was then poured into a mold (50mm×50mm×2mm) and placed at 65℃ for 30 minutes to form a gel. No water removal was required during the reaction. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining a chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances. When the pH value of the chitosan hydrogel membrane reaches 7.0±0.3, it can be considered that the removal is basically complete, thus obtaining a four-arm polyethylene glycol crosslinked chitosan hydrogel, which is the main body of the medicated patch.

[0062] The method for preparing the guide rod is as follows: First, pure nickel rods and pure titanium rods with a purity higher than 99.99% are selected and assembled into a consumable electrode by plasma arc welding in an argon-protected environment (assembly method: nickel rods and titanium rods are stacked alternately along the length to form a four-layer structure of "nickel-titanium-nickel-titanium" (each layer of single rods is not mixed, and the layers are arranged in the order of "nickel-titanium-nickel-titanium"). The four sides are sealed with plasma arc welding to make a consumable electrode with a cross-section of 40mm×40mm and a length of 300mm). The obtained consumable electrode was melted in a vacuum consumable solidification furnace (with the ultimate vacuum degree controlled to be ≤5×10). - The initial ingot was cast at 1580℃±10℃, with a melting current of 6.5kA, a voltage of 26V, and a melting rate of 1.2kg / min. After standing for 15s, the ingot was turned over and poured into a Φ120mm water-cooled copper mold. The ingot size was Φ120mm×300mm. After machining, peeling, and removing the riser, the composition was analyzed (analytical indicators: Ni 55.6–56.4wt%, O≤0.08wt%, H≤0.002wt%, C≤0.05wt%, Fe≤0.05wt%, Ti balance, total 100%), and a qualified ingot was obtained. Multiple ingots are welded together to form a composite electrode (welding method: multiple ingots are stacked coaxially along the axial direction and fixed by electron beam welding (vacuum degree ≤ 5×10). - The composite electrode was placed in a vacuum arc remelting furnace (VAR) for secondary melting (vacuum degree ≤ 1×10⁻²Pa, arc stabilizing current 4kA, melting rate 0.8kg / min). Under high vacuum, the melting rate and feeding time were precisely controlled (melting rate maintained at 0.8kg / min, current decreasing stepwise during feeding stage: 4kA→2kA→0.5kA, 5min per step, total feeding time 15min) to obtain a high-purity ingot with uniform composition (Ni 55.6-56.4wt%, O≤0.08wt%, H≤0.002wt%, Ti balance, total 100%), ensuring basic biocompatibility.

[0063] The high-purity ingot is heated to 850℃±10℃ in an electric resistance furnace (held for 90 minutes), then forged multiple times into a Φ30mm bar using a large-tonnage hydraulic high-speed forging machine, and the surface is ground. Next, it is precision forged to Φ10mm using a rotary forging machine, and then proceeds to the critical dimension reduction process: a multi-pass cold drawing process is adopted (each pass has a reduction rate ≤20%, specific passes: Φ10→Φ8.5→Φ7.2→Φ6.1→Φ5.2→Φ4.4→Φ3.7→Φ3.1→Φ2.6→Φ2.2→Φ1.8). When the cumulative deformation reaches 40%, intermediate vacuum annealing is performed at 750℃ (annealing time 30 minutes, vacuum degree ≤5×10). - During the process, powdered graphite lubricant (applied to the mold surface and the outer periphery of the rod) is used to reduce frictional loss and synergistically eliminate work hardening, gradually drawing the rod to the target diameter Φ1.8mm (tolerance ±0.02mm). The cold-drawn thin rod is vacuum annealed at 800-850℃ (balancing superelasticity and grain size), then the surface is polished by a centerless grinder (Ra≤0.2μm), cut to a standard length of 50±0.1mm by a CNC precision machine tool, and the end face is subjected to medical-grade passivation treatment (rounded R0.1mm to eliminate sharp edges); finally, it is sterilized by gamma irradiation and vacuum-sealed in a clean room environment to produce a guide rod with high fracture strength (>950MPa), superelasticity and fatigue resistance.

[0064] The preparation method of the tension strip is as follows: Polylactic acid (PLA) powder with a particle size ≤2 mm and calcium carbonate powder with a particle size of 2 μm were separately dried overnight in an 80℃ drying oven. The dried PLA particles and calcium carbonate powder were accurately weighed at a mass ratio of 98:2, placed in a mixer and mixed evenly, and then stored in a desiccator for later use. The uniformly mixed material was then fed into the mixer of a torque rheometer and melt-mixed for 12 minutes at a temperature of 160℃ and a rotor speed of 80 r / min to uniformly disperse calcium carbonate in the PLA matrix, thus obtaining the PLA-CaCO3 polylactic acid / calcium carbonate composite.

[0065] The polylactic acid and calcium carbonate composite PLA-CaCO3 was pulverized and uniformly pressed into PLA-CaCO3 fiber bundles with a thickness of 1.4 mm ± 0.05 mm on a flat vulcanizing apparatus (pressing process: heat preservation at 160℃ for 10 min, pressurization for 6 min, pressure 10 MPa, degassing 5 times: after each pressurization to 10 MPa, the pressure was immediately released to 0, with an interval of 30 s, and finally vacuum dried at 70℃ to constant weight).

[0066] In the preparation of the medicated patch, after the mixed solution is injected into the mold, one end (1 cm in length) of the PLA-CaCO3 fiber bundle is immediately embedded in the center of the mixed solution, while the other end (2 cm in length) remains exposed outside the mold. The mixture is then placed at 65°C for 30 minutes to form a gel, allowing the PLA-CaCO3 fiber bundle to bind to the gel through a dual mechanism of covalent cross-linking (Schiff base bonds) and physical entanglement. The medicated patch preparation process continues afterward, including removing the mold and allowing it to stand at room temperature to allow the reaction to complete, thus obtaining a chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, resulting in a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel, which is the medicated patch itself.

[0067] Performance testing: 1. Antibacterial performance test of the medicated patch itself: (1) Evaluation by inhibition zone method First, Gram-negative Escherichia coli (E. coli) was used as the target bacterium. The antibacterial activity of the prepared four-armed polyethylene glycol crosslinked chitosan hydrogel was evaluated by the intuitive inhibition zone method. The diameter of the inhibition zone directly reflects the antibacterial performance of the material.

[0068] Test method: The bacterial suspension (1×10⁸ CFU / mL) was spread on an agar plate using the agar diffusion method. After placing the gel sample, the plate was incubated at 37°C for 24 hours, and the diameter of the inhibition zone was measured.

[0069] During the test, four groups were used: acidic chitosan hydrogel group, basic chitosan hydrogel group, 4r-PEG-CHO variable group, and 4r-PEG-NH2 variable group, as detailed below: Acidic chitosan hydrogel group: Chitosan was dissolved in a 1% acetic acid solution (meaning 1g of acetic acid in 100mL of solution) to prepare acidic chitosan hydrogels with chitosan concentration gradients of 0.5%, 1%, 2%, and 3%. The results are as follows. Figure 4 (a)

[0070] Alkaline chitosan hydrogels: Chitosan was dissolved in an alkaline solvent system (lithium hydroxide LiOH, potassium hydroxide KOH, urea, and deionized water in a mass ratio of 4.5:7:8:80.5) to prepare alkaline chitosan hydrogels with chitosan concentration gradients (0.5%, 1%, 2%, 3%). The results are as follows. Figure 4 (b)

[0071] 4r-PEG-CHO variable group: Fix the concentration of 4r-PEG-NH2 (m = 0) (i.e., without 4r-PEG-NH2), and adjust the concentration of 4r-PEG-CHO. Here, n represents the actual concentration of 4r-PEG-CHO in the reaction solution (mol / L) as 0.003×n (n = 0, 1, 2, 4), corresponding to C0-N0, C1-N0, C2-N0, C4-N0, and the results are as Figure 4 shown in (c) below.

[0072] 4r-PEG-NH2 variable group: Fix the concentration of 4r-PEG-CHO (n = 1) (i.e., fix the concentration of 4r-PEG-CHO at 0.003 mol / L), and adjust the concentration of 4r-PEG-NH2. Here, m represents the actual concentration of 4r-PEG-NH2 in the reaction solution (mol / L) as 0.003×m (m = 0, 1, 2, 4), corresponding to C1-N0, C1-N1, C1-N2, C1-N4, and the results are as Figure 4 shown in (d) below.

[0073] Note: For the above four groups, except for the variation of the above variables, the others are the same as the preparation method of the medicated patch body of the present invention.

[0074] As Figure 4 shown in (a) below, Figure 4 shown in (b) below, the chitosan hydrogel prepared with an alkaline solution shows better antibacterial performance than the sample prepared with an acidic solution, and the antibacterial zone of the alkaline chitosan hydrogel is larger. Depending on the different concentrations of 4r-PEG-CHO and 4r-PEG-NH2 added, Figure 4 in (c) below, Figure 4 in (d) below, n and m respectively correspond to 0.003 times the concentrations of 4r-PEG-CHO and 4r-PEG-NH2 in the reaction solution (mol / L). For example, when synthesizing the four-arm polyethylene glycol cross-linked chitosan hydrogel, the concentrations of 4r-PEG-CHO and 4r-PEG-NH2 are 0.003 mol / L and 0.006 mol / L respectively. It can be seen that when the concentration of 4r-PEG-CHO is determined, with the addition of 4r-PEG-NH2, the antibacterial performance of the gel is enhanced.

[0075] (2) Analysis of dead-live bacteria activity of Escherichia coli When analyzing the dead-live bacteria activity of Escherichia coli, the group settings are as follows: Control group: Mix the Escherichia coli suspension with an equal volume of sterile water and culture them at 37°C for 6 hours and 12 hours respectively; Among them, the preparation method of the Escherichia coli suspension is to add the activated Escherichia coli to the LB liquid medium and culture it at 37°C until OD600 = 0.6 (equivalent to a concentration of 108 CFU / mL).

[0076] Four-arm polyethylene glycol cross-linked chitosan hydrogel treatment group: Escherichia coli suspension was mixed with an equal volume of four-arm polyethylene glycol cross-linked chitosan hydrogel extract, and cultured at 37°C for 6 hours and 12 hours, respectively. The four-arm polyethylene glycol crosslinked chitosan hydrogel extract is the mixed solution obtained in step (2) of this invention.

[0077] The results are as follows Figure 5 As shown, Figure 5 This study demonstrates the dead-to-live bioactivity analysis of *E. coli*, where dead bacteria emit red fluorescence, while live bacteria emit green fluorescence. Figure 5 In the middle (a), the fluorescence image of the control group after 6 hours of culture shows a large number of green fluorescent dots (live bacteria), indicating normal bacterial proliferation. Figure 5 (b) is the fluorescence image of the control group after 12 hours of culture. The number of green fluorescent dots increased significantly, further confirming the active growth of bacteria. Figure 5 Image (c) shows the fluorescence image of the four-arm polyethylene glycol cross-linked chitosan hydrogel treated group after 6 hours of cultivation. Almost all of the field of view consists of red fluorescent dots (dead bacteria), with only a few sporadic green fluorescent dots remaining. Figure 5 Image (d) shows the fluorescence image of the four-armed polyethylene glycol cross-linked chitosan hydrogel treatment group after 12 hours of cultivation. Red fluorescent spots still dominate, while green fluorescence almost completely disappears. Compared to the control group, the four-armed polyethylene glycol cross-linked chitosan hydrogel treatment group showed significant bactericidal effects at both 6 and 12 hours, with an extremely high proportion of dead bacteria, demonstrating that this chitosan gel possesses rapid and sustained excellent antibacterial ability against Escherichia coli.

[0078] (3) Antibacterial performance test against Staphylococcus aureus Staphylococcus aureus, a typical Gram-positive bacterium, is widely present in skin wound environments. This study also investigated the antibacterial properties of a four-armed polyethylene glycol cross-linked chitosan hydrogel against Staphylococcus aureus.

[0079] The group settings are as follows: Control group: PBS buffer solution; Experimental group: Four-arm polyethylene glycol crosslinked chitosan hydrogel; Control group: Staphylococcus aureus bacterial suspension was mixed with an equal volume of sterile water and incubated at 37°C for 6 hours and 12 hours, respectively. The method for preparing Staphylococcus aureus bacterial suspension is to add activated Staphylococcus aureus to LB liquid medium and incubate at 37°C until OD600=0.6 (equivalent to a concentration of 10⁸ CFU / mL).

[0080] Experimental group: Staphylococcus aureus bacterial suspension was mixed with an equal volume of four-arm polyethylene glycol cross-linked chitosan hydrogel extract and cultured at 37°C for 6 hours and 12 hours, respectively. The four-arm polyethylene glycol crosslinked chitosan hydrogel extract is the mixed solution obtained in step (2) of this invention.

[0081] like Figure 6 As shown, the OD value test results are similar to those of the E. coli experiment, confirming that the gel has good bactericidal ability.

[0082] (4) Minimum inhibitory concentration test Experimental groups: Six concentration gradients of four-arm polyethylene glycol cross-linked chitosan hydrogel extract were set up, with concentrations of 0, 20, 40, 60, 80, and 100 mg / 10 mL.

[0083] Staphylococcus aureus bacterial suspension was mixed with different concentrations of four-arm polyethylene glycol cross-linked chitosan hydrogel extract and cultured at 37°C for 24 hours.

[0084] The specific procedure was as follows: Plate counting was used for detection. The absorbance of the Staphylococcus aureus bacterial suspension at 600 nm (UV-Vis) was optimized to approximately 0.6. The bacterial suspension was then diluted 10,000 times with sterile water, and a four-arm polyethylene glycol cross-linked chitosan hydrogel extract was added to achieve the set concentration n (n = 0-100 mg / 10 mL). After thorough mixing and standing for 10 minutes, 100 μL of the suspension was evenly spread onto the surface of an agar medium. The agar medium was then incubated at 37°C for 24 hours.

[0085] The four-arm polyethylene glycol crosslinked chitosan hydrogel extract is the mixed solution obtained in step (2) of this invention.

[0086] Minimum inhibitory concentration test results are as follows Figure 7 As shown, Figure 7 In (a), the concentration is 0 mg / 10 mL, and the colonies grow densely. Figure 7 In (b), the concentration was 20 mg / 10 mL, and the number of colonies was significantly reduced. Figure 7 In the middle (c) sample, the concentration was 40 mg / 10 mL, and the number of colonies was further reduced. Figure 7 In the middle (d) sample, the concentration was 60 mg / 10 mL, and only a few scattered colonies remained. Figure 7 In the middle (e) sample, the concentration was 80 mg / 10 mL, and the colonies were extremely sparse. Figure 7In (f), at a concentration of 100 mg / 10 mL, no significant colony growth was observed after 24 hours of incubation. With increasing concentration of the four-armed polyethylene glycol cross-linked chitosan hydrogel extract, the number of Staphylococcus aureus colonies decreased significantly, exhibiting a clear concentration-dependent antibacterial effect. Complete sterilization was achieved when the gel concentration reached 100 mg / 10 mL. In summary, the prepared four-armed polyethylene glycol cross-linked chitosan gel dressing demonstrates excellent antibacterial activity against both Gram-negative and Gram-positive bacteria.

[0087] 2. Cytotoxicity test of four-arm polyethylene glycol polymer cross-linked chitosan hydrogel: To evaluate the biocompatibility of the prepared four-arm polyethylene glycol crosslinked chitosan hydrogel, mouse fibroblasts (L929 cells) were used for testing using the standard MTT assay; experimental and control groups were set up: The experimental group consisted of L929 cells co-cultured with a four-arm polyethylene glycol cross-linked chitosan hydrogel, while the control group consisted of L929 cells co-cultured with PBS buffer solution.

[0088] The specific steps are as follows: In the experimental group, a four-arm polyethylene glycol cross-linked chitosan hydrogel extract was added to DMEM standard culture medium supplemented with 10% fetal bovine serum into 96-well tissue culture plates. After forming a hydrogel of 0.5 cm long × 0.5 cm wide × 0.3 cm high, viable cells were counted and seeded into the culture plates, ensuring a cell suspension density of 6 × 10⁴ cells per 100 μL. The plates were then incubated in a 5% CO₂ incubator at 37°C for 24, 72, and 120 hours.

[0089] The difference between the control group and the experimental group was that the four-arm polyethylene glycol cross-linked chitosan hydrogel extract was replaced with an equal amount of PBS buffer solution; all other aspects were the same.

[0090] Upon reaching the predetermined time point, the cells were stained with calcein-AM (labeling live cells, emitting green fluorescence) and propidium iodide (labeling dead cells, emitting red fluorescence), and observed and recorded using a fluorescence microscope. The results are as follows: Figure 8 and Figure 9 As shown.

[0091] Figure 8 (a) is a fluorescence image of the experimental group after 24 hours of culture, showing a large number of green fluorescent cells, indicating good cell viability; Figure 8 (b) is a fluorescence image of the experimental group after 72 hours of culture. The density of green fluorescent cells increased significantly, indicating that the cells continued to proliferate. Figure 8 The middle image (c) shows the fluorescence image of the experimental group after 120 hours of culture. The number of green fluorescent cells has increased further, indicating that the cells still maintain good activity after long-term culture.

[0092] Figure 9 Corresponding results: Quantitative analysis of the percentage increase in viable cell growth rate at different time points in the experimental and control groups showed no significant difference between the cell growth rate in the experimental and control groups. The results indicate that L929 cells cultured in the four-arm polyethylene glycol cross-linked chitosan hydrogel extract maintained high activity at different time points, with green fluorescence significantly increasing with prolonged incubation time and a continuous increase in the number of viable cells, confirming the good biocompatibility of this gel material.

[0093] 3. Mechanical property testing of nickel-titanium alloy guide rods Tests were conducted according to the "YS / T 1147-2016 Tensile Test Method for Hyperelastic Nickel-Titanium Materials" at three temperature environments: -10℃, 20℃, and 40℃. The mechanical properties of the nickel-titanium alloy guide rods were tested and compared at these three temperature environments to verify the hyperelastic (SE) properties of this material. An AGX-V10 KN universal testing machine was used, with a 1kN pneumatic flat-push clamp for holding the rods. The testing speed was 3 mm / min. When the strain reached 6%, the force was unloaded to 7 MPa at a speed of 3 mm / min. Finally, the rods were stretched to fracture at a speed of 30 mm / min. The entire test was conducted in a constant temperature environment. This test was used to test the tensile strength and residual strain of the nickel-titanium alloy under different temperature conditions. The residual strain in this test is the difference between the strain value when unloaded to 7 MPa and the strain value corresponding to the initial loading to 7 MPa. The residual strain represents the magnitude of the plastic change of the material after loading and unloading. The greater the residual strain, the greater the plastic deformation of the material during the stretching process. The deformation is irreversible and it is less likely to recover its original shape. The smaller the residual strain, the smaller the plastic deformation during the stretching process. The easier it is for the material to recover its original shape.

[0094] Table 1 shows the experimental results: Regarding tensile strength, it gradually decreases with increasing temperature. However, overall, temperature has a relatively small effect on the tensile strength of nickel-titanium alloys. As for residual strain, at -10℃ and 20℃, the residual strain is generally within 5%. However, when the temperature reaches 40℃, the residual strain changes significantly, remaining within 0.5%, demonstrating the memory property of nickel-titanium alloys, i.e., superelasticity. It can be inferred that at -10℃ and 20℃, the plastic deformation caused by tension does not recover under stable temperature conditions, suggesting that the temperature for stabilizing the austenite phase has not yet been reached. When the temperature reaches 40℃, the nickel-titanium alloy exhibits recovery after tension, suggesting that the temperature for austenite phase stabilization has been reached.

[0095] Table 1. Test results of the hyperelastic mechanical properties of nickel-titanium alloy guide rods at different temperatures. Note: The first digit of the test number (1, 2, 3) represents the temperature group, and the second digit (1, 2, 3) represents the serial number of the repeated test within the same temperature group. For example, "1-1", "1-2", and "1-3" indicate that three repeated tests were conducted at -10℃ to verify the repeatability and reliability of the experimental results.

[0096] 4. Mechanical property testing of polylactic acid-calcium carbonate composite material Powdered polylactic acid (PLA) and calcium carbonate (CaCO3) were separately dried overnight in an 80°C drying oven. They were then mixed uniformly in different proportions and stored in a desiccator. The PLA-CaCO3 composites were prepared by melting and kneading the different mass ratios of PLA and CaCO3 in the mixer of a torque rheometer at 160°C and 80 r / min for 12 min. The added CaCO3 mass fractions were 2%, 5%, and 7% of the PLA mass (i.e., PLA to CaCO3 mass ratios of 98:2, 95:5, and 93:7, respectively), and the resulting composites were labeled PLA-CaCO3-2, PLA-CaCO3-5, and PLA-CaCO3-7, respectively.

[0097] Preparation of PLA and PLA-CaCO3 composite test samples: Pure PLA and PLA-CaCO3 mixtures with different composition ratios were pulverized and pressed into test samples with a thickness of 1.4 mm ± 0.05 mm on a flat vulcanizing apparatus. These samples were then cut into dumbbell-shaped strips (7 cm long and 1 cm wide) according to the standard (ASTM Standard D638). Tensile properties were tested according to the national standard GB / T1040-1992. The strips were subjected to tensile tests on an electronic universal testing machine under constant temperature and humidity conditions (23℃ ± 2℃, relative humidity 50% ± 5%) to determine tensile strength and elongation at break. The tensile speed in the tensile test was 5 mm / min, and the average value of the results from 5 strips was taken.

[0098] The results are as follows Figure 10 As shown, Figure 10 Figure (a) shows that compared with pure PLA, the addition of CaCO3 can improve the tensile strength of the composite material. The increase is 25.7% when 2% CaCO3 is added, 32.2% when 5% is added, and the increase is not significant (only 6%) when 7% is added. Low content (0%) and 5% CaCO3 have a reinforcing effect on PLA and good interfacial bonding performance. Figure 10As shown in Figure (b), the effect of CaCO3 on the elongation at break of the composite material is different from that on the tensile strength. The elongation at break is the largest when the CaCO3 content is 2% (7.54%), which is higher than that of PLA (6.02%). When the content is greater than 2%, the elongation at break gradually decreases. At 7%, it is still higher than that of PLA without CaCO3 (6.28%). This indicates that within a certain content range, CaCO3 causes the molecular chains of the composite to become entangled, and PLA-CaCO3-2 has the best elongation performance. Figure 10 As shown in (c), the PLA-CaCO3-5 composite containing 5% CaCO3 has the highest elastic modulus (457.6E), which is significantly greater than that of pure PLA (411.0E). The elastic modulus of the 2% CaCO3 composite (423.8E) is slightly higher than that of PLA, while the elastic modulus of the 7% CaCO3 composite (PLA-CaCO3-7) (372.2E) is significantly lower. Figure 10 Figure (d) shows that the maximum load of PLA composites after the introduction of CaCO3 changes with CaCO3 content in a similar trend to the elongation at break. The maximum loads of 2%, 5%, and 7% CaCO3 mixed into the PLA matrix are all significantly higher than those of pure PLA (478.4). The maximum load of PLA-CaCO3-2 composite is the highest (666.8), which is 39.4% higher than that of PLA. The maximum loads of PLA-CaCO3-5 and PLA-CaCO3-7 are 36.4% and 34.5% higher than that of PLA, respectively.

[0099] Comprehensive analysis shows that the introduction of CaCO3 enhances the mechanical properties of PLA. The 5% CaCO3 composite shows the greatest improvement in tensile properties and elastic modulus, while the 2% CaCO3 composite exhibits the highest elongation at break and maximum load. The weaker mechanical properties of the 7% CaCO3 composite are related to the lower interfacial forces. As a medicated patch pull strip, a certain degree of toughness is required. Considering factors such as tensile strength, elongation at break, and elastic modulus, the 2% CaCO3 composite is the most suitable choice for the pull strip.

[0100] Clinical application Indications: Superficial infection at the catheter exit site (infection depth ≤5mm); postoperative recovery period at the peritoneal dialysis catheter exit site, etc.

[0101] Contraindications: History of severe allergy to any of the ingredients in this patch (including chitosan, polylactic acid, etc.) or antibiotic allergy (skin prick test required); allergy to seafood or crustacean products; deep abscess or necrotizing fasciitis; coagulation disorders, platelet count <50×10⁻⁶. 9 / L; unable to cooperate with patch replacement and care procedures due to impaired consciousness, mental illness, etc.; outer polyester sleeve dislodgement leading to catheter displacement, dysfunction, or inability to use the catheter normally, etc. Detailed operation steps: 1. After disinfecting the skin, gently push the guide rod of the device of the present invention (handle end facing outward, medicated patch body wrapped and implanted end facing inward) along the axial direction of the peritoneal dialysis catheter to a predetermined depth in the superficial infection area of ​​the catheter exit, so that the medicated patch body is in close contact with the superficial infection area of ​​the peritoneal dialysis catheter exit. 2. Rotate the guide rod to unfold the multi-layer composite patch body and adjust the traction strip. Simultaneously adjust the externally reserved traction strip (control the exposed length of the end of the traction strip to 2cm). After ensuring that the patch body fully adheres to the skin and the catheter outlet, remove the guide rod. 3. After 12 hours of continuous use, lift the pull bar and pull out the entire device along with the pull bar, and replace it with a new device of the present invention (i.e., repeat steps 1-2). Replace it every 12 hours, and the total usage period shall not exceed 7 days.

[0102] Operating Precautions: 1. This procedure must be performed in a sterile environment to avoid contact with unsterilized areas; 2. The adjustment range of the tension bar should be ≤2mm / time to prevent over-tensioning; 3. When the depth of infection is >5mm, surgical debridement is required.

[0103] Storage conditions: The medicated patch should be stored away from light (temperature 2-8℃, humidity 30-50%), and has a shelf life of 24 months.

[0104] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device, characterized in that, Includes the patch itself, guide rod, and pull strip; The tip of the guide rod is fixedly connected to the right side of the patch body; The upper part of the pull strip is fixedly connected to the lower part of the patch body; The patch body is a four-armed polyethylene glycol polymer cross-linked chitosan hydrogel; The guide rod is a nickel-titanium alloy guide rod; The tension strip is made of polylactic acid and calcium carbonate composite material.

2. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 1, characterized in that, The preparation method of the medicated patch body is as follows: Step (1), Preparation of alkaline chitosan solution: Accurately weigh lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water in a mass ratio of 4.4-4.6:6.8-7.2:7.8-8.2:80-81, mix them and stir at room temperature to form a homogeneous mixed solvent; Then, under stirring conditions, chitosan, accounting for 1.4%-1.6% of the total mass of the homogeneous mixed solvent, is slowly added; after the chitosan has been added, stirring continues to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at -29°C to -31°C. After freezing, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution. Step (2), Preparation of alkaline chitosan hydrogel dressing: First, prepare an aqueous solution of 4r-PEG-NH2 with a concentration of 2.9wt%-3.1wt% and an aqueous solution of 4r-PEG-CHO with a concentration of 2.9wt%-3.1wt%. Then, under stirring conditions, 2.9wt%-3.1wt% aqueous solution of 4r-PEG-NH2 and 2.9wt%-3.1wt% aqueous solution of 4r-PEG-CHO were added sequentially to the alkaline chitosan solution prepared in step (1), and then the mixture was stirred to obtain a mixed solution. The ratio of the volume of the alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in 4r-PEG-NH2 with a concentration of 2.9wt%-3.1wt%, and the molar amount of 4r-PEG-CHO in the 4r-PEG-CHO aqueous solution with a concentration of 2.9wt%-3.1wt% is 98mL-102mL: 0.0006mol: 0.0003mol; The mixed solution was then injected into a mold and placed at 64℃-66℃ to react and form a gel. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining an alkaline chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, thereby obtaining a four-armed polyethylene glycol crosslinked chitosan hydrogel, which is the main body of the medicated patch.

3. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 2, characterized in that, The specific method of step (1) is as follows: Preparation of alkaline chitosan solution: accurately weigh lithium hydroxide (LiOH), potassium hydroxide (KOH), urea and deionized water in a mass ratio of 4.5:7:8:80.5, mix them and stir at 300 rpm for 30 minutes at room temperature to form a homogeneous mixed solvent; Then, under continuous stirring at 500 rpm, chitosan accounting for 1.5% of the total mass of the homogeneous mixed solvent was added within 60 minutes; after the chitosan was added, stirring was continued at 500 rpm for 1 hour to obtain a swollen chitosan alkaline solution. Next, the swollen chitosan alkaline solution was frozen at -30°C for 6 hours; then, it was thawed at room temperature and stirred continuously until it became a transparent solution. Finally, the transparent solution was centrifuged to remove bubbles and obtain a homogeneous solution, which is the alkaline chitosan solution.

4. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 2, characterized in that, The specific method for step (2) is as follows: First, prepare a 3wt% aqueous solution of 4r-PEG-NH2 and a 3wt% aqueous solution of 4r-PEG-CHO. Then, under stirring at 400 rpm, 3 wt% 4r-PEG-NH2 aqueous solution and 3 wt% 4r-PEG-CHO aqueous solution were added sequentially to the alkaline chitosan solution prepared in step (1), and then the mixture was stirred at 600 rpm for 10 minutes to obtain a mixed solution. The ratio of the volume of the alkaline chitosan solution, the molar amount of 4r-PEG-NH2 in a 3wt% 4r-PEG-NH2 solution, and the molar amount of 4r-PEG-CHO in a 3wt% 4r-PEG-CHO aqueous solution is 100mL: 0.0006mol: 0.0003mol. The mixture was then poured into a mold and placed at 65°C for 30 minutes to form a gel. Next, the mold is removed and allowed to stand at room temperature to allow the reaction to complete, thus obtaining a chitosan hydrogel membrane. Finally, the obtained chitosan hydrogel membrane is removed and repeatedly immersed in deionized water to remove internal alkaline substances, thereby obtaining a four-arm polyethylene glycol crosslinked chitosan hydrogel, which is the main body of the medicated patch.

5. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 4, characterized in that, The mold dimensions are 50mm×50mm×2mm; it is repeatedly immersed in deionized water to remove internal alkaline substances. When the pH value of the chitosan hydrogel membrane reaches 7.0±0.3, a four-arm polyethylene glycol crosslinked chitosan hydrogel is obtained.

6. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 1, characterized in that, The preparation method of the guide rod is as follows: Step A: First, select pure nickel rods and pure titanium rods with a purity higher than 99.99% and weld them into consumable electrodes by plasma arc welding in an argon-protected environment. Step B involves melting and casting the consumable electrode obtained in Step A into an initial ingot using a vacuum consumable solidification furnace. After machining, peeling, and removing the riser, the composition is analyzed to obtain a qualified ingot. Step C: Weld the ingots obtained from multiple steps B into a composite electrode, and put the composite electrode into a vacuum arc remelting furnace for secondary melting. Adjust the melting rate and feeding time to obtain a high-purity ingot with uniform composition. Step D involves heating the high-purity ingot to 850℃±10℃ in a resistance furnace and holding it at that temperature. The ingot is then forged to a Φ30mm rod and its surface is ground. Next, it is precision forged to Φ10mm and then transferred to a critical dimension reduction process to gradually draw the rod to the target diameter. Afterward, it is vacuum annealed at 800-850℃, followed by surface polishing, cutting to the standard length, and medical-grade passivation treatment on the end face. Finally, it is sterilized by gamma irradiation and vacuum-sealed in a cleanroom environment to obtain the guide rod.

7. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 6, characterized in that: In step A, the assembly welding method is to alternately stack nickel rods and titanium rods along the length direction to form a four-layer structure of nickel-titanium-nickel-titanium, and then seal the four sides with plasma arc welding to make a consumable electrode with a cross-section of 40mm×40mm and a length of 300mm. In step B, during vacuum consumable solidification furnace melting, the ultimate vacuum degree is controlled to be ≤5×10⁻⁶. - The melting pressure was 2 Pa, the melting current was 6.5 kA, the voltage was 26 V, and the melting rate was 1.2 kg / min. During casting, the casting temperature was 1580℃±10℃. After standing for 15 seconds, the casting was turned over and poured into a Φ120 mm water-cooled copper mold. The ingot size was Φ120 mm × 300 mm. The analysis of the composition required the following indicators: Ni 55.6-56.4 wt%, O≤0.08 wt%, H≤0.002 wt%, C≤0.05 wt%, Fe≤0.05 wt%, Ti balance, total 100%. In step C, during assembly welding, multiple ingots are coaxially stacked along the axial direction and fixed by electron beam welding, with a vacuum degree ≤5×10⁻⁶. - ²Pa, beam current 60mA, welding speed 200mm / min; during secondary melting, vacuum degree ≤1×10 -2 Pa, stabilizing arc current 4kA, melting rate 0.8kg / min; when adjusting melting rate and feeding time, the melting rate is maintained at 0.8kg / min, and the current decreases stepwise during the feeding stage: 4kA→2kA→0.5kA, each step lasting 5min, for a total feeding time of 15min; high purity ingot specifications: Ni 55.6–56.4wt%, O≤0.08wt%, H≤0.002wt%, Ti balance, total 100%; In step D, the high-purity ingot is heated to 850℃±10℃ in a resistance furnace and held for 90 minutes. It is then forged multiple times into a Φ30mm bar using a large-tonnage hydraulic high-speed forging machine, and the surface is ground. Next, it is precision forged to Φ10mm using a rotary forging machine and then transferred to the critical dimension reduction process. The critical dimension reduction process adopts a multi-pass cold drawing process. When the cumulative deformation reaches 40%, it is subjected to intermediate vacuum annealing at 750℃. During this process, powdered graphite lubricant is used to reduce friction loss, and the bar is gradually drawn to the target diameter Φ1.8mm±0.02mm. Then, it is vacuum annealed at 800-850℃, and then the surface is polished to Ra≤0.2μm by a centerless grinder. It is then cut to a standard length of 50±0.1mm by a CNC precision machine tool, and the end face is subjected to medical-grade passivation treatment, requiring a rounding R0.1mm to eliminate sharp edges. Finally, it is sterilized by gamma irradiation and vacuum sealed in a clean room environment to produce a guide rod with a fracture strength >950MPa.

8. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 7, characterized in that: The multi-pass cold drawing process is as follows: the shrinkage rate of each pass is ≤20%, and the specific passes are: Φ10→Φ8.5→Φ7.2→Φ6.1→Φ5.2→Φ4.4→Φ3.7→Φ3.1→Φ2.6→Φ2.2→Φ1.8; During intermediate vacuum annealing, the annealing time is 30 minutes and the vacuum degree is ≤5×10. - ²Pa.

9. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 2, characterized in that, The preparation method of the tension strip is as follows: S1: Powdered polylactic acid and calcium carbonate powder with a particle size ≤2mm were placed in a drying oven at 79℃-81℃ and dried overnight. The dried polylactic acid particles and calcium carbonate powder were mixed evenly at a mass ratio of 97.8-98.2:

2. The mixture was melt-kneaded at 158℃-162℃ under stirring to uniformly disperse calcium carbonate in the polylactic acid matrix, thus obtaining the polylactic acid / calcium carbonate composite PLA-CaCO3. S2: The polylactic acid and calcium carbonate composite PLA-CaCO3 was pulverized and uniformly pressed into PLA-CaCO3 fiber bundles with a thickness of 1.4mm±0.05mm on a flat vulcanizing apparatus. S3: During the preparation of the medicated patch, after the mixed solution is injected into the mold, one end of the PLA-CaCO3 fiber bundle is immediately embedded in the center of the mixed solution, while the other end of the PLA-CaCO3 fiber bundle is exposed outside the mold. Then, it is placed at 64℃-66℃ to react and form a gel, so that the PLA-CaCO3 fiber bundle is combined with the medicated patch.

10. The multi-layer composite peritoneal dialysis catheter outlet superficial infection control patch device according to claim 9, characterized in that, The specific method for S1 is as follows: Polylactic acid pulverized to a particle size ≤2mm and calcium carbonate powder with a particle size of 2μm were placed in an 80℃ drying oven and dried overnight. The dried polylactic acid particles and calcium carbonate powder were mixed evenly at a mass ratio of 98:2 and melt-mixed at a temperature of 160℃ and a rotor speed of 80r / min for 12 minutes to uniformly disperse calcium carbonate in the polylactic acid matrix, thus obtaining the polylactic acid / calcium carbonate composite PLA-CaCO3. In S2, the specific method of the pressing process is as follows: keep warm at 160℃ for 10 minutes, pressurize for 6 minutes, pressure is 10MPa, release air 5 times: after each pressurization to 10MPa, immediately release the pressure to 0, with an interval of 30s, and finally vacuum dry at 70℃ to constant weight.

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