Antibacterial and anti-adhesion double-balloon tracheal tube and preparation method thereof

Abstract

This invention provides an antibacterial and anti-adhesion double-balloon tracheostomy cannula and its preparation method. The invention involves constructing a coating material co-loaded with a newly developed tetradecyl antibacterial agent and chondroitin sulfate on both the cannula's surface and inner wall. This coating possesses both excellent hydrophilicity and strong antibacterial properties. The hydrophilicity makes it difficult for secretions to adhere; the antibacterial properties kill bacteria through contact, minimizing the development of drug resistance; and the anti-adhesion properties reduce the basis for biofilm formation. These three properties work synergistically to achieve full-chain protection from the "source" to the "process," significantly reducing the risk of luminal obstruction and VAP (ventilator-associated pneumonia), while also reducing the frequency of suctioning and mucosal damage, thus improving patient comfort.

Description

Technical Field

[0001] This invention relates to new medical materials, specifically to an antibacterial and anti-adhesion double-balloon tracheostomy cannula and its preparation method. Background Technology

[0002] The U.S. Centers for Disease Control and Prevention reports that nearly 1.7 million hospitalized patients contract infections from healthcare products each year while receiving treatment, and more than 98,000 patients (one in 17) die as a result. Venous thromboembolism is the second leading cause of morbidity and mortality in hospitalized children, accounting for 16% of all serious safety incidents. What can lead to venous thromboembolism? Figure 1 As shown, studies have revealed a correlation between infection and thrombosis. Compared to uninfected patients, infected patients have a 17.6% increased relative risk of thrombosis, with a 57% chance of thrombosis in patients with systemic bloodstream infections and a 27% chance in patients with localized infections. Further research indicates that blood-contact medical devices can potentially lead to the aforementioned infections. Taking tracheostomy cannulas as an example, existing tracheostomy cannulas have shown poor biocompatibility and related complications in long-term clinical use. Specifically, the surface of existing tracheostomy cannulas (including the inner and outer walls) easily adheres to respiratory secretions and bacterial biofilms, leading to venous thromboembolism, lumen obstruction, recurrent infections, and increased patient discomfort during suctioning.

[0003] Currently, to overcome the aforementioned problems, a tracheostomy tube with a surface coating has been introduced to address these issues. However, research has found that many coated tubes on the market use single-function coatings, such as those that are only hydrophilic or contain only silver ions for antibacterial properties. Furthermore, the coating is mostly concentrated on the outer surface, with insufficient attention paid to preventing adhesion to the inner wall of the tube. Moreover, current coating materials suffer from poor durability, easily detaching and failing under prolonged use and repeated suctioning. Additionally, long-term use of broad-spectrum antibacterial agents (such as silver ions) may induce bacterial resistance.

[0004] Furthermore, tracheostomy cannulas are also susceptible to pressure injuries caused by improper cuff management. Specifically, the pressure of a traditional single-cuff structure remains constant when the airway is inflated and closed, failing to adapt to dynamic changes in airway pressure. Excessive pressure can lead to tracheal mucosal ischemia, edema, ulceration, and even stenosis; insufficient pressure can cause air leakage, aspiration, and inadequate ventilation. The frequency of manual monitoring and adjustment of cuff pressure by healthcare workers is low, making precise control difficult.

[0005] Furthermore, tracheostomy cannulas suffer from insufficient monitoring of aspiration and reflux. Specifically, existing tracheostomy cannulas cannot monitor for aspiration or reflux of gastric contents in real time, delaying the diagnosis and treatment of aspiration pneumonia. Healthcare workers often only detect problems through clinical symptoms (such as decreased blood oxygen levels or elevated infection markers) or routine imaging examinations, which is often too late, increasing the risk to patients and the workload of healthcare professionals. Summary of the Invention

[0006] The present invention aims to overcome the above-mentioned defects and provide a multifunctional intelligent tracheostomy cannula that integrates active antibacterial and anti-adhesion, intelligent pressure regulation and early risk warning, so as to significantly reduce the incidence of related complications and improve patient comfort and medical safety.

[0007] This invention provides an antibacterial and anti-adhesion double-balloon tracheostomy cannula, which has the following characteristics: namely,

[0008] The inner and outer surfaces of the main body of the dual-balloon tracheostomy cannula are provided with antibacterial and anti-adhesion functional layers;

[0009] The antibacterial and anti-adhesion functional layer consists of chondroitin sulfate and tetradecyl imidazole sulfonate loaded on the inner and outer surfaces of the main tube of the dual-balloon tracheostomy cannula.

[0010] Furthermore, the present invention provides a method for preparing the above-mentioned antibacterial and anti-adhesion double-balloon tracheostomy cannula, comprising the following steps:

[0011] S1. A polydopamine layer containing active groups is formed on the surface of a substrate by utilizing the dopamine self-polymerization reaction, i.e., the PDA surface;

[0012] S2. Using polyallylamine, amino sites are introduced on the polydopamine layer to form a PDA-PAa surface;

[0013] S3. Under the action of an activator, chondroitin sulfate and tetradecyl imidazole sulfonate are simultaneously loaded onto the PDA-PAa surface of S2 to form a dual-balloon tracheostomy cannula with a PDA-PAa-C14 / CS functionalized surface.

[0014] Furthermore, the method for preparing the above-mentioned antibacterial and anti-adhesion double-balloon tracheostomy cannula provided by the present invention is further characterized in that:

[0015] In S1, the substrate surface is also pretreated;

[0016] The pretreatment involves plasma pretreatment of the substrate material.

[0017] Furthermore, the method for preparing the above-mentioned antibacterial and anti-adhesion double-balloon tracheostomy cannula provided by the present invention is further characterized in that:

[0018] The tetradecyl imidazole sulfonate salt is obtained by reacting NaSIPA with 1-tetradecyl-3-methylimidazolium bromide.

[0019] The tetradecyl imidazole sulfonate salt was prepared according to the method described in the literature "Catalytic Amounts of an Antibacterial Monomer Enable the Upcycling of Poly(Ethylene Terephthalate) Waste". Sodium 5-sulfoisophthalate (NaSIPA) (5.00 g, 0.0186 mol) was dissolved in 100 mL of deionized water, and 1-tetradecyl-3-methylimidazoli umbromide (5.00 g, 0.0139 mol) was added. The mixture was stirred vigorously for 2 hours, and the precipitate was collected by centrifugation.

[0020] Furthermore, the method for preparing the above-mentioned antibacterial and anti-adhesion double-balloon tracheostomy cannula provided by the present invention is further characterized in that:

[0021] The amount of tetradecyl imidazole sulfonate added shall not be less than 2‰ of the total weight of the substrate.

[0022] Furthermore, the method for preparing the above-mentioned antibacterial and anti-adhesion double-balloon tracheostomy cannula provided by the present invention is further characterized in that:

[0023] The amount of chondroitin sulfate added shall not be less than 50% of the total weight of the base material.

[0024] Furthermore, the aforementioned antibacterial and anti-adhesion double-balloon tracheostomy cannula is further characterized by:

[0025] A sensor layer is provided on the outer surface of the antibacterial and anti-adhesion functional layer on the outer surface of the double-balloon tracheostomy tube and / or on the inner surface of the subglottic suction tube.

[0026] The sensor layer is a chemical sensor;

[0027] The chemical sensor contains anthocyanins.

[0028] Furthermore, the aforementioned antibacterial and anti-adhesion double-balloon tracheostomy cannula is further characterized by:

[0029] The chemical sensor is loaded onto the tube body by immersing PVC in a dopamine solution under weakly alkaline conditions, causing the surface of the PVC to self-polymerize and form a polydopamine film. The PVC is then firmly bonded to the polydopamine film through π-π stacking, hydrogen bonding, or Michael addition reaction.

[0030] Furthermore, the aforementioned antibacterial and anti-adhesion double-balloon tracheostomy cannula is further characterized by:

[0031] The dual-balloon tracheostomy cannula also includes a dual-balloon assembly;

[0032] Dual airbag assembly, comprising a main airbag and a buffer airbag;

[0033] The main airbag and the buffer airbag are respectively installed on the main body, and their contraction and extension are independently controlled by the corresponding main airbag control mechanism and buffer airbag control mechanism.

[0034] Furthermore, the aforementioned antibacterial and anti-adhesion double-balloon tracheostomy cannula is further characterized by:

[0035] The main airbag control mechanism and the buffer airbag control mechanism are controlled by the central control mechanism, which drives the main airbag and the buffer airbag to contract and extend.

[0036] Pressure sensors are installed on both the main airbag and the buffer airbag;

[0037] The central control mechanism controls the main airbag control mechanism and the buffer airbag control mechanism to perform dynamic balancing operations according to the preset switching frequency;

[0038] The central control unit also controls the main airbag control mechanism and / or the buffer airbag control mechanism to regulate pressure based on the feedback information from the pressure sensors.

[0039] The function and effects of this invention:

[0040] This invention constructs a coating material co-loaded with a newly developed tetradecyl antibacterial agent and chondroitin sulfate on both the surface and inner wall of the cannula. This coating possesses both excellent hydrophilicity and strong antibacterial properties. The hydrophilicity makes it difficult for secretions to adhere; the antibacterial properties kill bacteria through contact, reducing the likelihood of drug resistance; and the anti-adhesion properties reduce the basis for biofilm formation. These three properties work synergistically to achieve full-chain protection from the "source" to the "process," significantly reducing the risk of lumen blockage and VAP (ventilator-associated pneumonia), while also reducing the frequency of suctioning and mucosal damage, thus improving patient comfort.

[0041] This invention also innovatively designs a comprehensive system integrating a dual-bladder structure with pressure sensing and feedback control, forming an "intelligent alternating inflation pressure microenvironment." When a patient coughs or a ventilator delivers air, causing a sudden increase in airway pressure, the system can instantly transfer some gas from the main airbag to the buffer airbag to prevent excessive local pressure; when the pressure drops, the gas flows back to ensure a seal. The alternating inflation of the upper and lower airbags achieves dynamic balance of airbag pressure, fundamentally preventing pressure injuries while ensuring a continuous and effective seal to prevent aspiration.

[0042] This invention also innovatively designs a visual early warning network. By setting up an anthocyanin network layer, it utilizes the reversible color changes of anthocyanins under different pH environments (e.g., colorless in a normal environment, reddish in an infected, acidified environment), making it a natural "chemical sensor." Medical staff can visually determine whether the microenvironment around the tracheostomy tube is prone to reflux and aspiration of digestive fluids using a simple built-in fiber optic observation lens. This low-cost, non-invasive early warning method enables timely intervention to detect reflux and aspiration in tracheostomy patients. Attached Figure Description

[0043] Figure 1 There is a correlation between infection and thrombosis;

[0044] Figure 2 A schematic diagram of the antibacterial and anti-adhesion double-balloon tracheostomy cannula provided in this embodiment;

[0045] Figure 3 A cross-sectional view of the main body of the antibacterial and anti-adhesion double-balloon tracheostomy cannula provided in this embodiment;

[0046] Figure 4 A schematic diagram of the antibacterial and anti-adhesion double-balloon tracheostomy cannula provided in this embodiment;

[0047] Figure 5 Contact angle test results of products prepared by different methods;

[0048] Figure 6 Antibacterial test results of products prepared by different methods, where A and B are in vitro antibacterial test results of direct contact method, and C is the antibacterial test result of adhesion method;

[0049] Figure 7 Antibacterial test results of products with different C14 addition amounts;

[0050] Figure 8 Cytotoxicity test results of products with different C14 addition amounts, where A is the result of in vitro antibacterial test by direct contact method, and B is the result of adhesion bactericidal test.

[0051] Figure 9 Results of blood compatibility and contact angle tests for products with different C14 addition amounts, where A represents the blood compatibility test result and B represents the contact angle test result;

[0052] Figure 10 Contact angle test results for products with different CS addition amounts;

[0053] Figure 11 Results of anticoagulant-protein adsorption test for products with different CS addition amounts;

[0054] Figure 12 Antibacterial test results of products with different CS addition amounts;

[0055] Figure 13 The results of cytotoxicity experiments for products with different CS addition amounts, where A is the cytotoxicity test result of the extract and B is the contact cytotoxicity result;

[0056] Figure 14 Results of blood compatibility tests on products with different CS addition amounts;

[0057] Figure 15 The product characterization spectrum of this embodiment;

[0058] Figure 16 Results of anticoagulation-protein adsorption test for products prepared by different methods; Detailed Implementation

[0059] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0060] Example 1. Antibacterial and anti-adhesion double-balloon tracheostomy cannula

[0061] This embodiment provides an antibacterial and anti-adhesion double-balloon tracheostomy cannula, such as Figure 2 As shown, it includes a main body 100 and a dual airbag assembly;

[0062] The dual-airbag assembly includes a main airbag 210 and a buffer airbag 220;

[0063] The main airbag 210 and the buffer airbag 220 are respectively mounted on the main tube 100, with the proximal airbag located at the upper part of the duct (2-3 cm from the opening) and the distal airbag located at the lower part (1-2 cm from the end). Low-tension silicone is used to reduce mucosal irritation. The contraction and extension of the main airbag 210 and the buffer airbag 220 are independently controlled by the corresponding main airbag control mechanism 211 and buffer airbag control mechanism 221. These two mechanisms are controlled by the central control mechanism to drive the main airbag 210 and the buffer airbag 220 to contract and extend.

[0064] The control mechanism of the aforementioned airbag can be a balloon-shaped device that draws in or releases air or liquid, or other devices that can inflate or flatten the airbag.

[0065] Both the main airbag 210 and the buffer airbag 220 are equipped with pressure sensors, which transmit the detected pressure signals to the central control mechanism in real time.

[0066] The central control mechanism controls the main airbag control mechanism and the buffer airbag control mechanism to perform dynamic balancing operations according to the preset switching frequency; for example, the module is set to alternately inflate the two airbags, with a switching time of 4 hours.

[0067] The central control mechanism also controls the main airbag control mechanism and / or the buffer airbag control mechanism to regulate pressure based on the feedback information from the pressure sensor. For example, the pressure during airbag inflation needs to be maintained at 20-30 cmH2O. When the pressure feedback from the pressure sensor is lower than this lower limit, intelligent inflation is performed. When it is higher than this upper limit, deflation is performed to maintain the set pressure range, thus forming a safe pressure strategy.

[0068] The main tube body is 100mm, made of medical-grade silicone SR or polyurethane, which has good biocompatibility, flexibility, and durability. The outer diameter of the tube is customized according to the patient's airway size, usually 8-10mm, while the inner diameter ensures smooth ventilation. Figure 3 As shown, the sensor layer 101 includes an antibacterial and anti-adhesion functional layer 100a loaded on its inner surface by techniques such as plasma treatment or chemical grafting, and an antibacterial and anti-adhesion functional layer 100b loaded on its outer surface, as well as a sensor layer 101 located on the outer surface of the double-balloon tracheostomy tube and / or on the outer surface of the antibacterial and anti-adhesion functional layer of the double-balloon tracheostomy tube and / or on the inner surface of the subglottic suction tube (the tube body shown by the arrow in the figure; in a preferred case, anthocyanins are loaded only on the inner surface of the tube body).

[0069] The main functional raw materials of the above-mentioned antibacterial and anti-adhesion functional layer are chondroitin sulfate CS and tetradecyl imidazole sulfonate C14, such as Figure 4 As shown, the specific preparation method is as follows:

[0070] S0. The substrate surface is also pretreated to incorporate active groups. Specifically, the gas-cutting sleeve material is ultrasonically cleaned 1-3 times in deionized water and ethanol. Subsequently, it undergoes plasma (air / oxygen plasma equipment) pretreatment for 3 minutes to incorporate hydrophilic active groups such as hydroxyl and carboxyl groups.

[0071] In some experimental cases, it was found that chondroitin sulfate CS and tetradecyl imidazole sulfonate C14 had inferior stability on the tube compared to the S0+S1 scheme when S0 was skipped and S1 was performed directly.

[0072] S1. Constructing a high-adhesion, high-density amination-modified polydopamine coating. The specific method is as follows: The pretreated substrate is immersed in a polydopamine PDA solution dissolved in Tris-HCl buffer (2 mg / mL dissolved in Tris-HCl solution at pH 8.5), and allowed to stand for 24 hours. This allows the dopamine self-polymerization reaction to form a polydopamine layer containing active groups on the substrate surface, i.e., the PDA surface. Subsequently, after rinsing and drying with deionized water, the resulting PDA surface is immersed in an alkaline polyallylamine (PAa) aqueous solution (prepared using a 2 wt% solution of 15 wt% polyallylamine solution with a Mw~3000 concentration) for 12 hours. It is then rinsed again with deionized water. Using polyallylamine, amino sites are introduced onto the polydopamine layer, ultimately obtaining the PDA-PAa surface.

[0073] In some experimental cases, without S0+S1 testing, it was found that chondroitin sulfate CS and tetradecyl imidazole sulfonate C14 had extremely poor stability on the tube body and were easily flushed away in the early stage of tube placement, and subsequently could not achieve the expected anti-adhesion and antibacterial effects.

[0074] S2. Based on a multi-step assembly and chemical grafting strategy, an antibacterial and hydrophilic bifunctional coating was constructed. The specific method is as follows: (1) Preparation of chemically mediated bifunctional coating precursor solution: C14 was dissolved in ethanol and deionized water was added to prepare a stock solution. CS (the amount of CS added is 50-80% of the mass of polydopamine and polyallylamine previously deposited on the substrate) and C14 (the amount of C14 added is not less than 2‰ of the total weight of the substrate) stock solution were added to the MES buffer solution (0.025 mg / mL NaCl and 0.0195 mg / mL MES dissolved in aqueous solution). Subsequently, EDC and NHS were added to activate the carboxyl groups (EDC is about 1.15 times the mass of CS, and NHS is about 1.5 times the mass of EDC). The pH of the solution was adjusted to acidic (preferably pH 6) with NaOH and stirred for 30-60 min (preferably 30 min), and then the pH was raised to alkaline (preferably pH 8) with NaOH.

[0075] (2) Construction of polydopamine coating and bifunctional coating grafting: Immerse the pre-coated PDA-PAa surface in this solution and react for a period of time (preferably 2 hours). Thoroughly rinse the resulting PDA-PAa-(C14-CS) surface with deionized water and dry it in an oven.

[0076] The preferred dosage of CS is not less than 50%, and the preferred dosage of C14 is not less than 2‰.

[0077] The sensor layer is a mixture of anthocyanins and polydopamine in a 1:0.1-5 (mass) ratio. Under weakly alkaline conditions, the tube is immersed in a dopamine solution, causing its surface to self-polymerize and form a polydopamine film (as above). Due to the strong adhesion and abundant catechol / amino functional groups of the PDA layer, it can serve as an ideal intermediate layer. Subsequently, anthocyanins are firmly bonded to the PDA layer through π-π stacking, hydrogen bonding, or Michael addition reactions. Notably, when it is located on the outer surface of the antibacterial and anti-adhesion functional layer of the dual-balloon tracheostomy cannula, there is no need to form a PDA layer again; anthocyanins can be loaded directly after the loading of C14 and CS.

[0078] It can also be woven into a mesh layer on the outer surface of the antibacterial and anti-adhesion functional layer 100b using similar techniques such as electrospinning or injection molding. Color changes can be directly observed through the transparent area of ​​the duct wall, or the signal can be transmitted to an external display through a built-in fiber optic sensor to achieve real-time alarm.

[0079] Comparative Experiment 1: Adjusting the order of C14 addition

[0080] The control group is as follows:

[0081] SR: Single tube;

[0082] SR-PDA: SR tube activated by PDA;

[0083] SR-PDA-PAa: Activated by PDA and PAa, without loading any drugs or reagents;

[0084] SR-PDA-(PAa-C14): After activation by PDA and PAa, only C14 is loaded;

[0085] SR-PDA-PAa-CS: After activation by PDA and PAa, only CS is loaded;

[0086] SR-PDA-(PAa-C14)-CS: After activation by PDA and PAa, C14 is loaded first and then CS is loaded;

[0087] SR-PDA-PAa-(C14-CS): In this test, Example 1, CS was 80% and C14 was 2‰.

[0088] A. Contact angle test:

[0089] Experimental methods: The surface chemical composition of the samples was measured using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR, Nicolet 6700, USA) and X-ray photoelectron spectroscopy (XPS, ESCALABQXi, USA). The hydrophilicity and surface morphology of the coating were measured using a water contact angle analyzer (DSA100, Germany) and scanning electron microscopy (SEM, JSM-7800F, China), respectively.

[0090] The results are as follows Figure 5 As shown, the SR-PDA-PAa coating exhibits hydrophobicity, possibly because the hydrophilic groups (-NH2) are buried during deposition, exposing the hydrophobic Paa backbone (-CH2-CH2-). Both the SR-PDA-(PAa-C14)-CS and SR-PDA-PAa-(C14-CS) coatings show good hydrophilicity, but the SR-PDA-(PAa-C14)-CS coating is less hydrophilic than the SR-PDA-PA-(C14-CS) coating, possibly because the C14 group is buried along with the hydrophilic groups.

[0091] B. Antibacterial test:

[0092] (1) Direct contact in vitro antibacterial method: The central venous catheter was cut into 2 cm lengths and then sterilized with ultraviolet light for 30 minutes before use. The bacteria were resuspended twice with PBS to remove the culture medium, and the bacterial concentration was adjusted to 1*106 CFU / mL with PBS again. The sample was placed in 2 mL of bacterial suspension and incubated at 37°C for 18 hours. After incubation, the sample was removed and gently rinsed three times with PBS to remove loose bacteria on the surface. The sample was then placed in 2 mL of PBS and sonicated for 20 minutes to separate the surface-adhered bacteria. After serial dilution, the sample was plated for counting.

[0093] like Figure 6 As shown in A and 6B, based on the comparison results of SR-PDA-(PAa-C14)-CS and SR-PDA-PAa-(C14-CS), it can be found that the SR-PDA-(PAa-C14)-CS coating does not exhibit antibacterial properties, while the SR-PDA-PAa-(C14-CS) coating exhibits good antibacterial properties.

[0094] (2) Adhesion sterilization: The sample was sterilized under UV light for 15 minutes in advance; the bacteria in the culture medium were harvested by centrifugation and resuspended in PBS at a concentration of 1108 CFU / mL. The sterilized sample was placed at the bottom of a 24-well plate, and 2 mL of the above bacterial suspension was added to the corresponding well. The plate was shaken and co-cultured for 18 h. The sample was removed and the surface was gently rinsed with sterile PBS solution to remove excess bacteria from the upper layer. The sample was then transferred to a plate containing 2 mL of PBS and sonicated for 2 minutes to separate the adhering bacteria. The sample was then serially diluted and plated for counting.

[0095] like Figure 6 As shown in Figure C, the bacterial counts in the SR-PDA-Pa-C14 and SR-PDA-Pa-(C14-GS) groups were significantly reduced in the *S. aureus* experiment, indicating that these two materials had significant adhesion and bactericidal effects against *S. aureus*. In the *E. coli* experiment, the bacterial counts in the SR-PDA-Pa-C14 and SR-PDA-Pa-(C14-GS) groups were also significantly reduced; however, SR-PDA-Pa-(C14-GS) exhibited better adhesion and bactericidal ability.

[0096] C. Anticoagulation properties – Protein adsorption test: Results are as follows Figure 16 As shown, SR-PDA-PAa-(C14-CS) exhibits significant advantages.

[0097] Comparative Experiment Example 2. Adjustment of C14 Addition Amount

[0098] The amount of chondroitin sulfate added was fixed at 20%, and the amount of deposited C14 (0-2‰) was adjusted.

[0099] A. Antibacterial test: The antibacterial effect was tested, and the results are as follows: Figure 7 As shown, the antibacterial performance gradually improves with the increase of C14 content, and the antibacterial rate of over 99.9% can be basically achieved at 2‰.

[0100] B. Cytotoxicity test: The prepared samples coated with different concentrations of antibacterial agent (0-2‰) were immersed in PBS for 24 hours (37℃) and the extract was extracted for cytotoxicity test.

[0101] Cytotoxicity test method: Preparation: 1*1cm 2 Sample, 24-well plate, bacterial suspension (10 9 ), PBS, SYTO-9, PI; Experimental group: 0.25‰, 0.5‰, 1‰, 2‰ C14, Control group: SR.

[0102] The samples were sterilized under UV light for 15 minutes beforehand; bacteria were harvested from the culture medium by centrifugation, washed with PBS solution, and resuspended in PBS at a concentration of 10. 8CFU / mL. Place the sterilized sample at the bottom of a 24-well plate, add 200 μL of the above bacterial suspension to the corresponding well, and co-incubate with shaking for 18 h. Gently rinse the surface with sterile PBS solution to remove excess bacteria from the upper layer. Prepare 1 mL of PBS solution containing 0.1% SYTO-9 and 0.1% PI as the staining solution. Spread 500 μL of the staining solution onto the surface of the sample to be tested, and stain at 37°C in the dark for 15 minutes. After staining, aspirate the excess staining solution and gently rinse with sterile PBS solution. Place the sample test surface in a confocal dish and photograph it using a laser confocal microscope (600x and 1000x oil immersion).

[0103] The results are as follows Figure 8 As shown in a, when the C14 dosage is 2‰, 100% cell viability can still be maintained.

[0104] The coated films containing different concentrations of antibacterial agents (0-2‰) were brought into contact with the cells after they had grown on the substrate.

[0105] The results are as follows Figure 8 As shown in b, compared with "PristineSR" (without antibacterial agent), the cell viability of the 0.25‰ C14 group was significantly increased; the viability of the 0.5‰ C14 group decreased somewhat; the viability of the 1‰ C14 group increased significantly again; and the viability of the 2‰ C14 group decreased significantly. Overall, the antibacterial agent exhibited a fluctuating effect on cell viability within the concentration range of 0-2‰, showing an initial increase followed by a decrease, then an increase again, and finally a decrease, without significantly inhibiting cell viability at any concentration.

[0106] C. Blood compatibility test:

[0107] Experimental method: Preparation: 1.5*2cm 2 Sample, defibrinated sheep blood, 1.5 mL centrifuge tube, 10 mL centrifuge tube, PBS, water, centrifuge tube (containing waste liquid), negative control group, positive control group, blank control group, and C14 experimental groups with different concentrations of 0.25‰, 0.5‰, 1‰, and 2‰.

[0108] Red blood cells were collected by centrifuging 2 mL of defibrinated sheep blood at 4°C and 3000 rpm for 5 minutes, and washed twice with PBS solution. The solution was then diluted to 10 mL with PBS. 1 mL of red blood cell dilution solution and the sample (0.5 mL red blood cell dilution solution + 0.5 mL sample) were added to each centrifuge tube. Pure PBS solution was used as a negative control, and ultrapure water as a positive control. The mixture was incubated at room temperature for 4 hours. Finally, the system was centrifuged at 4°C and 8000 rpm, photographed, and the UV-Vis absorbance of the supernatant at 570 nm was measured.

[0109] The results are as follows Figure 9As shown in figure a, for the 0.25‰~2‰ C14 group: the hemolysis rate is approximately 0%, and the green dashed line in the figure marks "Non-hemolytic," indicating that these materials have no risk of hemolysis and good blood compatibility. That is, regardless of the amount of C14 used, it is not compatible with blood.

[0110] D. Contact Angle Experiment: Thin films coated with different concentrations of antibacterial agent (0-2‰) were brought into contact with red blood cells grown on a plate. The results are as follows: Figure 9 As shown in b, 0.25‰ C14: contact angle 38.4° (hydrophilic, liquid can partially spread); 0.5‰ C14: contact angle 42.9° (hydrophilic, slightly higher than the 0.25‰ group); 1‰ C14: contact angle 26.6° (enhanced hydrophilicity, better liquid spreadability); 2‰ C14: contact angle 16.1° (strong hydrophilicity, liquid spreads rapidly on the surface). In other words, C14 modification significantly reduces the contact angle of the material, transforming it from strongly hydrophobic to hydrophilic, and the higher the C14 concentration, the stronger the hydrophilicity.

[0111] Comparative Experiment 3. Adjusting the amount of CS added.

[0112] The amount of C14 added was fixed at 2‰, and the amount of deposited chondroitin sulfate CS (20%~80%) was adjusted.

[0113] A. Contact Angle Experiment: All coatings were equilibrated in PBS for 10 minutes, dried, and the contact angle was measured. Figure 10 As shown, coatings with 50% and 80% CS addition have a contact angle of ~0°, exhibiting better hydrophilicity.

[0114] B. Anticoagulation-protein adsorption test: such as Figure 11 As shown, the anticoagulant performance improves with increasing CS content.

[0115] C. Antibacterial test: such as Figure 12 As shown, the antibacterial performance improves with increasing CS content.

[0116] D. Cytotoxicity assay:

[0117] Cytotoxicity of the extract: The sample was immersed in 1 mL of PBS solution and incubated at 37°C for 24 h to obtain the extract. The revived cells were seeded into 96-well plates and cultured for 12 h (plate coating). After 24 h, the culture medium in the 96-well plates was discarded, and 100 µL of cell culture medium was added. Different concentration gradients of extract (100 µL, 75+25, 50+50, 25+75) were added and cultured for 12 h. The culture medium was discarded, and 100 µL of PBS solution was added for washing. The PBS solution was discarded, and 100 µL of 10% CCK-8 solution was added. After 4 h of culture, the absorbance of the solution at 450 nm was detected by microplate reader.

[0118] like Figure 13 As shown in Figure a, the cell viability of all samples was close to 100%, indicating that these materials (including SR composites with different proportions of CS) have extremely low cytotoxicity and good biocompatibility.

[0119] Contact cytotoxicity: The compatibility of samples with HeLa cells was assessed using a CCK-8 assay kit. For direct contact cytotoxicity testing, samples were sterilized under UV light for 15 minutes and then placed in 24-well plates. Subsequently, HeLa cells were seeded onto the sample surface into the wells. The culture plates were incubated at 37°C with 5% CO2 for 24 hours. After incubation, cell viability was assessed using a CCK-8 assay kit.

[0120] like Figure 13 As shown in b, in the 20% CS group, cell viability decreased to approximately 85%, indicating mild cytotoxicity; in the 50% CS group, cell viability recovered to approximately 110% (higher than the control group), indicating that this concentration of CS has cell compatibility and may even promote cell activity; in the 80% CS group, cell viability returned to approximately 100%, comparable to the original material, with no significant cytotoxicity. In other words, 20% CS has mild cytotoxicity; 50% CS and 80% CS have good cell compatibility (the 50% CS group showed the best viability).

[0121] E. Blood compatibility test:

[0122] The results are as follows Figure 14 As shown, regardless of the dosage of CS, it is not compatible with blood.

[0123] Example 2. Characterization

[0124] like Figure 15 As shown,

[0125] SR-PDA coating: Dopamine oxidative self-polymerization forms polydopamine, whose aromatic ring C=C stretching vibration (adding 1575, 1540 cm⁻¹) -1 ) and CN stretching vibration (added 1469cm) -1 ).

[0126] SR-PDA-PAa coating: The primary amine group (-NH2) of PAa undergoes a Schiff base reaction with the quinone structure of PDA to form an imine bond (C=N) (1576cm). -1 and 1540cm -1 Peak enhancement).

[0127] SR-PDA-(PAa-C14)-CS / SR-PDA-PAa-(C14-CS) coating: CS and C14 were successfully grafted, 1645cm -1 The peak value on the left and right sides is enhanced, and it is 3366.93cm.-1 The broad peaks indicate the presence of numerous OH / NH hydrogen bonds on the surface.

Claims

1. An antibacterial and anti-adhesion double-balloon tracheostomy cannula, characterized in that: The inner and outer surfaces of the main body of the dual-airbag tracheostomy tube are provided with antibacterial and anti-adhesion functional layers. The antibacterial and anti-adhesion functional layer consists of chondroitin sulfate and tetradecyl imidazole sulfonate loaded on the inner and outer surfaces of the main tube of the dual-balloon tracheostomy cannula.

2. The method for preparing an antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 1, characterized in that, It includes the following steps: S1. A polydopamine layer containing active groups is formed on the surface of a substrate by utilizing the dopamine self-polymerization reaction, i.e., the PDA surface; S2. Using polyallylamine, amino sites are introduced on the polydopamine layer to form a PDA-PAa surface; S3. Under the action of an activator, chondroitin sulfate and tetradecyl imidazole sulfonate are simultaneously loaded onto the PDA-PAa surface of S2 to form a dual-balloon tracheostomy cannula with a PDA-PAa-C14 / CS functionalized surface.

3. The method for preparing an antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 1, characterized in that: In S1, the substrate surface is also pretreated; The pretreatment involves plasma pretreatment of the substrate material.

4. The method for preparing an antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 1, characterized in that: The tetradecyl imidazole sulfonate salt was obtained by reacting NaSIPA with 1-tetradecyl-3-methylimidazolium bromide.

5. The method for preparing an antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 1, characterized in that: The amount of tetradecyl imidazole sulfonate added is not less than 2‰ of the total weight of the substrate.

6. The method for preparing an antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 1, characterized in that: The amount of chondroitin sulfate added shall not be less than 50% of the total weight of the substrate.

7. The antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 1, characterized in that: A sensor layer is provided on the outer surface of the antibacterial and anti-adhesion functional layer on the outer surface of the double-balloon tracheostomy tube and / or on the inner surface of the subglottic suction tube. The sensor layer is a chemical sensor; The chemical sensor contains anthocyanins.

8. The antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 4, characterized in that: The chemical sensor is loaded onto the tube body by immersing PVC in a dopamine solution under weakly alkaline conditions, causing the surface of the PVC to self-polymerize and form a polydopamine film, which is then firmly bonded to the polydopamine film through π-π stacking, hydrogen bonding, or Michael addition reaction.

9. The antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 1, characterized in that: The dual-airbag tracheostomy cannula also includes a dual-airbag assembly; The dual-airbag assembly includes a main airbag and a buffer airbag; The main airbag and the buffer airbag are respectively installed on the main body, and their contraction and extension are independently controlled by the corresponding main airbag control mechanism and buffer airbag control mechanism.

10. The antibacterial and anti-adhesion double-balloon tracheostomy cannula as described in claim 9, characterized in that: The main airbag control mechanism and the buffer airbag control mechanism are controlled by the central control mechanism, which drives the main airbag and the buffer airbag to contract and extend. Pressure sensors are installed on both the main airbag and the buffer airbag. The central control mechanism controls the main airbag control mechanism and the buffer airbag control mechanism to perform dynamic balancing operations according to a preset switching frequency. The central control mechanism also controls the main airbag control mechanism and / or the buffer airbag control mechanism to perform pressure regulation based on the feedback information from the pressure sensor.

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