Central venous catheter that prevents clot and infection formation

Abstract

The present disclosure relates to central venous catheters used in the healthcare sector, and comprises coating the surfaces of temporary central catheters with multilayer film structures containing resveratrol and acetylsalicylic acid groups to form a nanocomposite structure providing antibacterial properties and clot-formation preventing activity. By means of the strong antioxidant and anti-inflammatory properties of resveratrol and the antiplatelet effect of acetylsalicylic acid, antimicrobial properties are imparted to the catheter surface, and the risk of infection development during long-term catheter use is reduced.

Description

[0001] CENTRAL VENOUS CATHETER THAT PREVENTS CLOT AND INFECTION FORMATION

[0002] Technical Field

[0003] The present disclosure relates to central venous catheters used in the healthcare sector, and concerns the coating of the surfaces of temporary central catheters with groups containing resveratrol and acetyl salicylic acid with multiple film layers so as to form a nano composite structure to provide antibacterial properties and thrombus formation-preventing effectiveness.

[0004] Background of the Invention

[0005] Today, catheters placed into one of the arms, neck or groin regions are central venous catheters. Patients who generally stay in the intensive care unit and individuals who receive drug treatment for a long time benefit from this type of catheter. This catheter, which is important for monitoring vital functions, facilitates the administration of serum and the drawing of blood. Central venous catheters (CVCs) are an invasive method frequently used for critical functions such as haemodynamic monitoring and the administration of fluids and drugs. However, dysfunctions may occur in the performance of these catheters over time. Among the main causes of these dysfunctions are clot formation, mechanical reasons and infection. When aseptic techniques are not followed during the placement of the catheter, bacteria from the external environment may reach the surface of the catheter and then enter the vascular system. This situation may lead to sepsis after catheter placement. An infected catheter increases the risk of systemic infection by allowing bacteria and other pathogens to pass into the bloodstream. As a result, the length of hospital stay of patients increases, and healthcare costs rise. The risk of infection also increases when proper care and monitoring are not carried out during the use of a CVC. If the catheter is not regularly cleaned and hygiene rules have not been followed at its connection points, bacterial colonisation may occur. In addition, long-term use of the catheter is another factor that increases the risk of infection.Long-term catheters may increase the risk of infection particularly by causing the formation of fibrin layers and clots. Therefore, in order to reduce the risk of infection in central venous catheter applications, the use of appropriate aseptic techniques and regular monitoring after catheter placement and catheter care are of great importance. The implementation of infection control measures in hospitals plays a critical role in preventing infections associated with CVCs. Clot formation is one of the most common causes of central venous catheter dysfunction. Blood clots may form on the inner surface of the catheter, preventing fluid passage. This situation is affected by factors such as the material of the catheter, blood flow rate and the patient’s coagulation status. Especially in long-term use, fibrin layers accumulate inside and around the catheter, and this reduces blood flow and makes it difficult to use the catheter effectively. Infection is another important factor associated with the dysfunction of central venous catheters. It carries a risk of infection due to bacteria entering from the region where the catheter is placed. When an infection develops, vascular occlusion or loss of catheter function may occur as a result of inflammation. Such infections may also adversely affect the general condition of the patient. Therefore, meticulous application of aseptic techniques during catheter placement and regular catheter care are critically important to reduce the risk of infection. Infections associated with central venous catheters constitute a large portion of hospital admissions and increase mortality and morbidity in patients as a cause of sepsis.

[0006] Central venous catheter infections are generally associated with bacteria found in the skin flora. The most common bacterial pathogens are as follows:

[0007] 1. Staphylococcus aureus: Both methicillin-resistant (MRSA) and methicillinsensitive (MSSA) strains are among the most common causes of central venous catheter infections. This bacterium, which is found on the skin and mucosal surfaces, may cause infection during or after catheter placement.

[0008] 2. Coagulase-negative Staphylococci (CNS): Especially, Staphylococcus epidermidis plays an important role in catheter-associated infections. These bacteria are generally found in the skin flora and are frequently associated with long-term catheter use.

[0009] 3. Enterobacteriaceae: Bacteria such as E. coll and Klebsiella species are associated with urinary tract and gastrointestinal infections but may also causecentral venous catheter infections, particularly in cases of multi-combined infections.

[0010] 4. Pseudomonas aeruginosa: This bacterium is frequently observed, particularly in patients with immunodeficiency and in intensive care units. It is an important risk factor as a cause of central venous catheter infections.

[0011] 5. Candida spp.: Among fungal infections, especially in long-term catheter use, Candida species may also be among the infection sources. Such infections are generally more common in immunocompromised patients. In addition to these bacteria, mycobacteria and other gram-negative bacteria may also be among the rare causes of central venous catheter infections.

[0012] Thrombosis is the clotting of blood within a vessel to form a clot (thrombus) and generally occurs on or within the surfaces of blood vessels. Thrombosis associated with central venous catheters (CVCs) is the result of a series of complex events arising from both factors affecting the vascular structure and haemostatic mechanisms. The formation of thrombosis may be explained in detail through the following steps:

[0013] 1. Vascular Endothelial Damage: The first stage of thrombosis is generally the injury of the vascular endothelium. During the placement of a central venous catheter or when it moves within the vessel, the tip of the catheter or the catheter itself may damage the vessel wall. Endothelial damage enables platelets and coagulation factors to adhere more effectively to the vessel surface, which initiates the clotting process.

[0014] 2. Platelet Activation and Aggregation: Damage to the vascular endothelium triggers the adhesion and activation of platelets to the vessel. Activated platelets release chemical substances such as serotonin, ADP, and thromboxane A2, causing more platelets to be attracted to the area and adhere to one another. Platelet aggregation forms the initial structure of the clot.

[0015] 3. Coagulation Pathway: The activation of platelets not only initiates the initial response but also triggers the blood coagulation cascade. There are two main coagulation pathways: the extrinsic pathway (tissue factor pathway) and the intrinsic pathway (contact activation pathway). Both pathways activatethrombin, which enables the conversion of fibrinogen into fibrin. Fibrin maintains the structural integrity of the clot by holding the platelets together.

[0016] 4. Fibrin Deposition and Clot Formation: Fibrin forms a mesh-like structure in the area where thrombosis develops and further holds existing platelets together, increasing the stabilisation of the clot. As the clot grows within the blood flow, its size increases and carries a risk of embolism. Clotting inside and around the catheter may affect the functionality of the catheter and impede blood flow. 5. Changes in the Vessel Wall: As thrombosis progresses, inflammatory changes occur in the wall of the affected vessel. This inflammation may lead to loss of elasticity and accumulation of inflammatory cells in the vessel wall. Over time, these changes may further deteriorate the structure and function of the vessel. Central venous catheter infections may increase the risk of thrombosis. Infection may trigger local inflammatory responses and cause changes in the vessel wall. This inflammation may affect blood flow and accelerate clotting processes. Particularly, bacterial or fungal infections may increase clot formation within the vessel and negatively affect both the risk of thrombosis and the functionality of the catheter. Consequently, these two conditions play a synergistic role in the dysfunction of central catheters.

[0017] In most cases, the prognosis in catheter-associated infection may progress quite severely, and preventing such infections is preferred rather than treating them. Ensuring that the catheter is placed by an experienced person, ensuring compliance with aseptic conditions during interventions, avoiding central venous catheterisation where possible, preventing the development of infection if catheterisation has been performed, and preventing complications if infection has developed are extremely important.

[0018] Various coating technologies have been developed for central venous catheters (CVCs) and other medical devices. These coating technologies are designed to reduce the risk of infection, increase bioactivity and improve the performance of catheters. Some prominent coating technologies are as follows:

[0019] 1. Antimicrobial Coatings: These coatings contain antimicrobial agents added to the surface or structure of the catheter. For example, antibiotics or antimicrobial substances used together with hydrophobic polymers or conductive polymersmay inhibit bacterial growth. Such coatings may significantly reduce the risk of infection.

[0020] 2. Fibrin and Advanced Polymeric Coatings: Fibrin-based coatings used in paper or tissue engineering applications may be utilised to increase the biocompatibility of the catheter. Such coatings support tissue integration and healing by facilitating the adhesion of cells to the coating.

[0021] 3. Silver and Copper Coatings: Silver and copper nanoparticles are used as coatings for various medical devices due to their natural antibacterial properties. In particular, silver coatings have emerged as an effective method for reducing bacterial contamination.

[0022] 4. Hydrophilic Coatings: Hydrophilic coatings provide a structure that facilitates flow along the catheter and prevents blood from adhering to the catheter surface. These coatings may improve blood flow within the vessel and reduce the risk of clotting.

[0023] 5. Biofilm-Preventing Coatings: Biofilm is a structure formed by bacteria adhering to a surface and increases the risk of infection. Biofilm-preventing coatings aim to reduce catheter infections by preventing the formation of these structures. Such coatings generally contain special molecular structures.

[0024] 6. Bioactive Glass Coatings: Bioactive glass and ceramic coatings support tissue regeneration in the region and increase biological interactions. Such coatings may strengthen tissue integration during long-term catheter use.

[0025] 7. Nanoparticle Coatings: Coatings developed using nanotechnology increase surface area due to the reduction of particle size, which may enhance coating effectiveness.

[0026] The document KR101775079B1 in the state of the art is titled “Catheter Containing Organic Germanium And Method For Preparing The Same”. This invention relates to a catheter containing organic germanium and a method for producing it, and more specifically to a catheter with a surface coated with organic germanium and to a method for producing the catheter. The catheter here is one in which organic germanium is incorporated into a polymer, and the surface of the polymer is coatedwith organic germanium. It was developed to suppress oxidative stress in cells or living tissues and to increase treatment efficiency.

[0027] The document US2005004554A1 in the state of the art is titled “Central Venous Catheter”. The central venous catheter consists of a catheter body having multiple lumens extending longitudinally within it. At least one of the lumens extends longitudinally from the proximal end of the catheter body to an exit port at its distal end, and at least one other lumen passes longitudinally through the catheter body to the closed distal portion of the catheter body. It does not contain any coating.

[0028] The document US2024082463A1 in the state of the art is titled “Coated Medical Product”. It relates to a suspension for coating medical devices containing at least one tri-O-acylglycerol, at least one taxane in microcrystalline form, and at least one solvent in which at least one tri-O-acylglycerol dissolves and in which the microcrystals of at least one taxane do not dissolve. It also relates to a method for preparing said suspension, a method for coating a medical device with said suspension, and medical devices coated with at least one tri-O-acylglycerol and at least one microcrystalline taxane.

[0029] Brief Description of the Invention

[0030] Resveratrol is a polyphenol compound naturally found in many plants. It is found in high amounts particularly in foods such as red wine, grapes, blueberries, raspberries and peanuts. It is a stilbene compound with the chemical formula (C14H12O3). It has two main types: trans-resveratrol and cis-resveratrol. Trans-resveratrol is the form that is more effective in terms of biological activities. With its antioxidant, anti-inflammatory, anticoagulant and antimicrobial properties, resveratrol may be useful in solving the problems frequently encountered in central venous catheters. The potential advantages and effects of a CVC coated with resveratrol are given below.

[0031] 1. Reducing the Risk of Infection: Central venous catheters may lead to serious infections such as catheter-associated bloodstream infections (CLABSI). Resveratrol has antimicrobial properties that inhibit the growth of various microorganisms and the formation of biofilm. Resveratrol may show potential effectiveness against the following pathogens: Staphylococcus aureus(particularly methicillin-resistant S. aureus - MRSA): It is a frequently encountered infectious agent in catheters, and resveratrol has been shown in some studies to be effective against this bacterium.

[0032] • Escherichia coir. E. coli, a gram-negative bacterium, may cause catheter infections. Resveratrol may inhibit its growth by attacking the bacterial cell wall.

[0033] • Pseudomonas aeruginosa: This is a resistant and biofilm-forming type of bacterium. Resveratrol may inhibit growth on the catheter surface by showing antibiofilm activity against this bacterium.

[0034] • Candida albicans: In patients with fungal infection, the antifungal effect of resveratrol may also be taken into consideration. Resveratrol may reduce biofilm formation by preventing bacteria from adhering to the surface.

[0035] Biofilm is a layer of bacteria that plays an important role in catheter infections and ensures that microorganisms are protected by adhering to the catheter surface. The resveratrol coating may disrupt this biofilm and reduce the risk of catheter infection.

[0036] 2. Reducing Thrombus Formation: Central venous catheters may trigger coagulation and lead to the formation of a thrombus (blood clot). A thrombus may cause catheter obstruction, embolism and complications such as thrombophlebitis. Resveratrol may prevent thrombus formation with its anticoagulant (anti-clotting) properties. Resveratrol is one of the compounds that inhibit platelet aggregation (the clustering of platelets that play a role in blood clotting). By preventing platelets from adhering to the catheter surface, it may reduce thrombus formation. In addition, resveratrol is known to improve the function of endothelial cells in vessel walls and reduce inflammation within the vessel. This situation may prevent the activation of clotting factors and therefore the formation of a thrombus.

[0037] 3. Anti-inflammatory Effects: Inflammation may develop in the region where the catheter is placed, and this situation may adversely affect the function of the catheter. By suppressing the inflammatory response, resveratrol reduces the production of pro-inflammatory cytokines (e.g. TNF-a, IL-6). Thus, it mayalleviate the inflammation that develops around the catheter, increase patient comfort and preserve catheter functionality.

[0038] 4. Antioxidant Effect: Resveratrol is known for its strong antioxidant properties.

[0039] Oxidative stress may cause cell damage and negatively affect tissue healing. Catheters coated with resveratrol may provide a protective effect against oxidative stress, accelerate tissue healing, and support better tolerance of the catheter by the body.

[0040] 5. Prolonging Catheter Lifespan: Microbial growth and biofilm formation on the catheter may limit catheter function and lead to frequent replacement. Catheters coated with resveratrol may prevent the proliferation of such microorganisms and ensure that the catheter is used safely for a longer duration.

[0041] 6. Additional Advantages for Cancer and Chemotherapy Patients: Resveratrol may offer potential benefits with its immune-supportive and antioxidant effects in cancer patients receiving chemotherapy. During chemotherapy treatment, infection risk is high in patients whose immune systems are weakened. Catheters coated with resveratrol may reduce these risks and improve the overall condition of patients.

[0042] The second substance to be used in coating the catheter is acetyl salicylic acid (ASA), and a central venous catheter (CVC) coated with this substance may provide various advantages, especially due to its antiplatelet, anti-inflammatory, and antimicrobial properties. ASA, more commonly known as aspirin, is a compound that stands out with its anti-clotting effects by inhibiting platelet aggregation. In terms of protecting catheters against complications such as clotting and infection, ASA coating may have some important potential benefits.

[0043] 1. Reducing Thrombus Formation: The formation of a thrombus (blood clot) in central venous catheters is a frequently encountered problem. The adhesion of blood cells and clotting factors to the surface of the catheter may obstruct blood flow and lead to catheter occlusion, intravascular thrombosis, and even the risk of embolism. The Anti-thrombotic Effect of ASA:

[0044] • Preventing Platelet Activation: Acetyl salicylic acid inhibits the cyclooxygenase-1 (COX-1 ) enzyme present in platelets and prevents theproduction of thromboxane A2. Thromboxane A2 is an important component that plays a role in platelet aggregation (coming together) and vasoconstriction. This inhibitory effect may prevent the adhesion of platelets to the catheter surface and clot formation.

[0045] • Improving Blood Flow: The inhibition of platelet aggregation by ASA increases blood fluidity and reduces thrombus formation. This enables the catheter to maintain its functionality for a longer duration.

[0046] Reducing the Risk of Infection: Central venous catheters carry a risk of causing infections by allowing bacterial and fungal pathogens to adhere to the catheter surface. Although the antimicrobial properties of ASA have not been comprehensively studied, its anti-inflammatory effects may indirectly reduce the risk of infection. Antimicrobial and Anti-inflammatory Effects:

[0047] • Suppressing Bacterial Growth: Acetyl salicylic acid has anti-inflammatory properties that have been shown in some studies to inhibit the growth of pathogens such as Staphylococcus aureus. This may be an important advantage, particularly in situations where catheter-associated infections are common.

[0048] • Reducing Biofilm Formation: Against biofilm formation, which is one of the main causes of infections, ASA may suppress biofilm formation and make it more difficult for bacteria to adhere to the catheter surface. Anti-inflammatory Effect: Long-term use of central venous catheters may cause inflammation around the vessel. Tissue irritation and inflammation are frequently observed in the region where the catheter is placed. The anti-inflammatory properties of ASA may reduce this inflammation and increase patient comfort. Reducing Inflammation:

[0049] • By inhibiting the COX-1 and cyclooxygenase-2 (COX-2) enzymes, ASA reduces the production of prostaglandins. Prostaglandins are an important mediator of the inflammatory response. A catheter coated with ASA may suppress the activity of these enzymes and thereby reduce the inflammatory response.• The suppression of inflammation may also prevent thrombus formation and tissue damage that may develop around the catheter.

[0050] 4. Prolonging Catheter Lifespan: Thrombi and infections may cause catheters to lose functionality over time and to require frequent replacement. ASA coating may allow the catheter to remain functional for a longer duration by preventing thrombus and biofilm formation. This means fewer catheter replacements for the patient and a reduction in related complications.

[0051] 5. Use in Chemotherapy and Other High-risk Patients: In patients receiving chemotherapy or other immunosuppressive treatments, the risks of infection and thrombosis are high. A catheter coated with ASA may reduce catheter- associated complications in these patients and make treatment processes safer.

[0052] 6. Cost and Ease of Application: ASA is a common and inexpensive drug.

[0053] Therefore, the production cost of such a coating may be relatively low. In addition, since aspirin has high biological compatibility, CVCs coated with ASA are also unlikely to cause biocompatibility issues.

[0054] The nano coating applications of resveratrol and acetyl salicylic acid for central venous catheters offer an innovative approach to reducing infection risk and increasing the effectiveness of bioactive components. While resveratrol possesses strong antioxidant and anti-inflammatory properties, acetyl salicylic acid is known for its anti platelet effect. The combination of these two compounds helps enrich the catheter surface with antimicrobial properties and reduces the risk of infection developing during long-term catheter use. By means of nano coating technology, the controlled release of these components is ensured, optimising the cellular responses in the region where the catheter is placed. The composite structure to be obtained by nano coating also has the potential to increase biocompatibility and protect the tissues surrounding the vessel where the catheter is placed. This application increases both the mechanical stability of the catheter and creates positive effects on cell adhesion and proliferation by regulating biological interactions. Thanks to the multilayer nano composite film structure, it will be possible for the effectiveness to continue throughout the duration of use in the patient. Consequently, the combination of resveratrol and acetyl salicylic acid offers an important innovative solution to increase the safety and effectiveness of central venous catheters and reduce infection rates in clinical applications.The Aims of the Invention

[0055] The aim of the invention is the reduction of infection risk by means of providing nano coating applications of resveratrol and acetyl salicylic acid for central venous catheters. The aim of the invention is the provision of antimicrobial properties to the catheter surface by means of the strong antioxidant and anti-inflammatory properties of resveratrol and the antiplatelet effect of acetyl salicylic acid, and the reduction of the risk of infection developing during long-term use of the catheter.

[0056] The aim of the invention is the optimisation of the cellular responses in the region where the catheter is placed by ensuring the controlled release of the components used by means of the nano coating technology of the catheter.

[0057] The aim of the invention is the increase of biocompatibility and the protection of the tissues surrounding the vessel where the catheter is placed by means of the composite structure to be obtained with nano coating.

[0058] The aim of the invention is both to increase of the mechanical stability of the catheter and to provide of a positive effect on cell adhesion and proliferation by regulating its biological interactions.

[0059] The aim of the invention is the provision of a catheter whose effectiveness continues throughout the duration of use in the patient by means of the multilayer nano composite film structure.

[0060] The aim of the invention is the increase of the safety and effectiveness of central venous catheters and the reduction of infection rates in applications by means of the combination of resveratrol and acetyl salicylic acid.

[0061] Detailed Description of the Invention

[0062] Characterisation studies were carried out to enable the coating of the central venous catheter by incorporating resveratrol and acetyl salicylic acid into the multilayer film structure. For this purpose, cationisation must be performed to obtain ionic charges on the central venous catheter surface. Polyethylenimine (PEI) may be used in the cationisation process, and after 25 minutes of treatment in a 3% solution prepared at pH 10, a drying process is carried out.The catheter, which is used in the healthcare sector, is placed inside large vessels, and used in long-term drug treatment, fluid administration, or blood sampling procedures, and which provides antibacterial and thrombus formation-preventing properties, is a central venous catheter. The surface of the central venous catheter contains resveratrol [3-cyclodextrin and acetyl salicylic acid at the nanoscale.

[0063] The method for obtaining a catheter that provides antibacterial and thrombus formation-preventing properties comprises the process steps of:

[0064] a. cleaning the catheter surface,

[0065] b. keeping the catheter surface in a cationic solution,

[0066] c. drying,

[0067] d. preparing a solution in anionic structure,

[0068] e. preparing a solution containing polyelectrolyte in cationic structure,

[0069] f. dipping into and keeping in the anionic solution,

[0070] g. washing,

[0071] h. dipping into and keeping in the cationic solution,

[0072] i. washing,

[0073] j. drying,

[0074] k. dipping into and keeping in acid solutions,

[0075] l. sterilising.

[0076] Step “a” is the step of cleaning the catheter surface with 70% alcohol for 5 minutes. Step “b” is the step of rendering the catheter surface cationic by keeping it at room temperature for 25 minutes in a 3% polyethylenimine solution at pH 10. Step “c” is the step of drying at 60<C for 10 minutes. Step “d” is the step of preparing a solution in anionic structure by placing resveratrol into [3-cyclodextrin capsules at pH 7.5. Step “e” is the step of preparing a solution containing polyelectrolyte in cationic structure with polydiallyldimethylammonium chloride (PDDA). Step “f” is the step of dipping into and keeping in the anionic resveratrol [3-cyclodextrin solution. Step “g” is the step of washing with deionised water for 5 minutes. Step “h” is the step of dipping into and keeping in the cationic PDDA solution. Step “i” is the step of washing with deionised water for 5 minutes. It also comprises the step of repeating steps “f”, “g”, “h”, “i”, “j”, “k” until the required number of layers is reached. Step “j” is the step of drying at GO'C for 30 minutes. Step “k” is the step of dipping into and keeping in acetyl salicylic acidsolutions at different concentrations in sequence. Furthermore, in step “k”, the acetyl salicylic acid solution is at 0.5% and / or 1% and / or 2% concentrations. Step “I” is the step of sterilisation with hot air at 1 SO'C for 3 m inutes.

[0077] Since resveratrol does not possess ionic charge, it is first placed inside [3-cyclodextrin capsules to render it ionically charged. Functionally, cyclodextrins may be considered as empty capsules, and compared with traditional encapsulation methods, their most important characteristic is that they effectively protect each molecule encapsulated. The physical, chemical and biological properties of compounds are significantly modified through encapsulation.

[0078] Resveratrol and 6-

[0079]

[0080] n

[0081] Solution Preparation: [3-Cyclodextrin (generally prepared at 1-2% w / v concentration) and resveratrol (in the range of 0.1 -0.5% w / v to increase solubility) are mixed together. The mixing process is carried out at room temperature or in heated water (40-50cC) using a magnetic stirrer or ultrasonication.

[0082] pH Adjustment: The stability of resveratrol and its capacity to form a complex with [3-cyclodextrin are optimised at pH 7-7.5. This pH is generally ensured with buffer solutions (for example, phosphate buffer).

[0083] Encapsulation: The mixture is stirred for 12-24 hours to make it homogeneous. Ultrasonication may be applied to increase encapsulation efficiency.

[0084] Zeta Potential Analysis: after encapsulation, the surface charge of the capsules is analysed through zeta potential measurements. The targeted pH range (6-8) is selected to provide an anionic character.Catheter Dipping and Coating Process:

[0085] Preparation of Solutions for Coating: Resveratrol-p-Cyclodextrin Solution: The previously prepared capsules are dissolved in pure water or a suitable buffer and then made ready for use at 0.1 -0.5% concentration.

[0086] PDDA Solution: PDDA is generally prepared at 0.5-1% w / v. Due to its cationic character, it is optimised to create a positive charge on the surface.

[0087] The appropriate pH value (pH 4.7-5.5) at which an anionic character will be exhibited is determined by zeta potential graphs and the suitable resveratrol structure for coating will be obtained. For providing the cationic layer, positively charged polyelectrolytes such as polydiallyldimethylammonium chloride (PDDA) are used. For multilayer film coating with resveratrol [3-cyclodextrin capsules and PDDA, positively charged catheters are dipped sequentially into the given solutions, and this process cycle is repeated until the desired number of layers is obtained. First, by dipping into the resveratrol [3-cyclodextrin capsules, the catheter with a cationic charge is coated anionically, and then by dipping into the PDDA solution, the surface with anionic charge is coated cationically. Thus, the layers are obtained. After the desired number of layers is reached, the multilayer films formed on the catheter will be dried at 60<C.

[0088] Dipping Process - Resveratrol-B-Cvclodextrin Capsule Coating:

[0089] Catheters with cationic surface charge are first dipped into the anionic resveratrol capsule solution for 5-15 minutes (the optimum duration is determined according to surface coating density).

[0090] PDDA Coating - The catheter coated with resveratrol capsules is dipped into PDDA solution for 5 minutes to obtain a positive charge. After the resveratrol capsule / PDDA coating processes with 20-40 multilayer films number, the catheters are dried at GO'C for 1-2 hours.

[0091] Acetyl Salicylic Acid Coating Process:

[0092] Solution Preparation:

[0093] Acetyl salicylic acid (ASA) is dissolved in a mixture of ethanol and pure water and prepared at concentrations of 0.5%, 1% and 2%.

[0094] The pH of the solutions (for example, within the range of 3-5) is adjusted for stability.Coating Process:

[0095] Catheters coated with resveratrol capsule / PDDAare dipped respectively into each ASA solution:

[0096] 0.5% ASA: Dipping duration is generally 5 minutes.

[0097] 1% ASA: Dipping duration is generally 5-10 minutes.

[0098] 2% ASA: Dipping duration is 10-15 minutes.

[0099] Intermediate drying may be applied at each stage and / or final drying may be carried out after all ASA dipping processes are completed. If sequential different ASA concentrations are not used, coating is carried out at a single concentration (for example, 2%) and the duration is kept constant (generally 10-15 minutes).

[0100] Final Drying and Sterilisation Process:

[0101] Drying:

[0102] After all dipping processes are completed, the catheters are dried at GO'C for 1-2 hours. This removes excess moisture on the surface and increases the stability of the coating.

[0103] Sterilisation:

[0104] For final sterilisation, the catheters are subjected to hot air sterilisation at ISO'C for 3 minutes. This duration and temperature are optimised so as not to compromise the coating properties.

[0105] Catheters coated with multilayer resveratrol [3-cyclodextrin capsules / PDDAare coated with acetyl salicylic acid at different concentrations by means of the dipping-removal principle. The final coated catheter structure is made ready by exposure to hot air sterilisation at ISO'C for 3 minutes.

[0106] The present disclosure comprises the coating of the surface of the central venous catheter with multilayer resveratrol and acetyl salicylic acid, which prevents clot and infection formation. The present disclosure comprises rendering the central venous catheter surface ionically charged, preparing [3-cyclodextrin capsules containing resveratrol and solutions containing acetyl salicylic acid, and coating the catheter surfaces sequentially first with multilayer films of resveratrol [3-cyclodextrincapsules / PDDA. It comprises the subsequent dipping-removal process with acetyl salicylic acid and the sterilisation process steps. The surface of the central venous catheter is rendered cationically charged by first cleaning with alcohol and keeping it in a 3% polyethylenimine solution for 25 minutes at room temperature. For the ionically charged resveratrol structure, the preparation of [3-cyclodextrin capsules and the examination of zeta potential curves ensure that the appropriate pH value is determined for the anionic layer. The multilayer coating of the central venous catheter with resveratrol [3-cyclodextrin capsules / PDDA comprises dipping the cationic catheter respectively into the solution containing resveratrol [3-cyclodextrin capsules and then into the solution containing PDDA by means of the dipping-removal method, continuing this cycle until the desired number of layers is obtained, and then drying at 60<C. Catheters coated with multilayer resveratrol [3-cyclodextrin capsules / PDDA comprise a coating with acetyl salicylic acid at different concentrations by means of the dipping-removal method and the sterilisation at 130<C.

Claims

CLAIMS1. A catheter used in the healthcare sector, which is placed inside large vessels and used in long-term drug treatment, fluid administration, or blood sampling procedures, and which provides antibacterial and thrombus formation-preventing properties, wherein it is a central venous catheter.

2. The catheter according to claim 1 , characterized by the surface of the mentioned central venous catheter comprising; nanoscale resveratrol [3-cyclodextrin and acetyl salicylic acid.

3. A method for obtaining a catheter that provides antibacterial and thrombus formation-preventing properties, characterized by comprising the process steps of:a. cleaning the catheter surface,b. keeping the catheter surface in a cationic solution,c. drying,d. preparing a solution in an anionic structure,e. preparing a solution containing a polyelectrolyte in a cationic structure, f. dipping into and keeping in the solution in the anionic structure,g. washing,h. dipping into and keeping in the solution in the cationic structure,i. washing,j. drying,k. dipping into and keeping in acid solutions, andl. sterilising.

4. The catheter production method according to claim 3 characterized by comprising; the process step of cleaning the catheter surface with 70% alcohol for 5 minutes in the step “a”.

5. The catheter production method according to claim 3, characterized by comprising; the process step of rendering the catheter surface cationic by keeping it in a 3% polyethyleneimine solution at pH 10 for 25 minutes at room temperature in the step “b”.

6. The catheter production method according to claim 3 characterized by comprising; the process step of drying for 10 minutes at 60 'C in the step “c”.

7. The catheter production method according to claim 3 characterized by comprising; the process step of preparing an anionic solution by placing resveratrol into p-cyclodextrin capsules at pH 7.

5. in the step “d”.

8. The catheter production method according to claim 3 characterized by comprising; the process step of preparing a cationic polyelectrolyte-containing solution with polydiallyldimethylammonium chloride (PDDA) in the step “e”.

9. The catheter production method according to claim 3 characterized by comprising; the process step of immersing the catheter in the anionic resveratrol- p-cyclodextrin solution and keeping it therein in the step “f”.10.The catheter production method according to claim 3 characterized by comprising; the process step of washing with deionised water for 5 minutes in the step “g”.

11. The catheter production method according to claim 3 characterized by comprising; the process step of immersing the catheter in the cationic PDDA solution and keeping it therein in the step “h”.12.The catheter production method according to claim 3 characterized by comprising; the process step of washing with deionised water for 5 minutes in the step “i”.13.The catheter production method according to claim 3 wherein the process steps “f”, “g”, “h”, “i”, “j”, and “k” are repeated until the required number of layers is obtained.14.The catheter production method according to claim 3 characterized by comprising; the process step of drying at 60 'C for 30 minutes in the step “j”.15.The catheter production method according to claim 3 characterized by comprising; the process step of immersing the catheter sequentially in acetylsalicylic acid solutions of different concentrations and keeping it therein in the step “k”.16.The catheter production method according to claim 3 or claim 12 wherein an acetylsalicylic acid solution having a concentration of 0.5% and / or 1% and / or 2% in the step “k”.17.The catheter production method according to claim 3 characterized by comprising; the process step of sterilising with hot air at 130 'C for 3 minutes in the step “I”.

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