Antibacterial catheter and preparation method thereof

Abstract

The invention provides an antibacterial catheter and a preparation method thereof. The antibacterial catheter comprises a catheter main body, the material of the catheter main body comprises silica gel, a solvent used in the preparation process of the antibacterial catheter comprises hexafluoroisopropanol, the catheter main body is swelled by using the solvent, and an antibacterial agent is dispersed in the catheter main body. The hexafluoroisopropanol has a good swelling effect on the catheter main body, so that the antibacterial agent can be well loaded on the catheter main body. And the preparation process is simple, so that when the antibacterial agent is dispersed in the catheter main body, additional basifier, penetrant or drug solubilizer (such as NaOH) and the like are not needed, and subsequent treatment such as heating or high-pressure sterilization and the like is also not needed.

Description

Technical Field

[0001] The invention relates to an antibacterial catheter and a preparation method thereof, belonging to the technical field of drainage catheters. Background Art

[0002] With the development of catheter diagnosis and treatment technology, the demand for medical catheters in clinical practice continues to increase, with nearly 10 million cases used each year. As a component of the shunt system, the ventricular external drainage catheter is used in cerebrospinal fluid drainage or shunt surgery for patients with hydrocephalus. During the process of catheter intervention in the human brain, bacteria can easily adhere to the surface of the catheter and rapidly proliferate to form bacterial biofilms, which can lead to medical infection accidents and, in severe cases, death of the patient. Therefore, the preparation of an ventricular external drainage catheter with anti-infection function has important clinical application value and significance.

[0003] At present, the swelling loading method and the surface coating method are mainly used to prepare external drainage catheters with antibacterial functions. For example, the invention patent application CN115154864A discloses an antibacterial and anti-adhesion super-slip drainage catheter, which uses the surface coating method to coat the outer surface of the drainage section of the catheter groove with polypyrrolidone, which combines with water molecules to form a layer of hydrogel film coating, which can largely prevent the deposition of bacteria, thereby playing an antibacterial role. However, the drainage catheter has the disadvantages of easy precipitation of biological proteins on the surface of the coated catheter and reduced antibacterial effect when implanted in the human body for a long time.

[0004] Commonly used solvents in the swelling loading method are dichloromethane, tetrahydrofuran, methanol and chloroform, and common antibacterial agents are rifampicin, clindamycin hydrochloride and minocycline. However, existing solvents have some shortcomings, such as poor photostability and high toxicity of chloroform, and poor swelling effect of methanol on the catheter body. In addition, a single solvent is often unable to dissolve multiple drugs at the same time, and it is even impossible to achieve uniform loading of multiple drugs on the catheter. Even if multiple solvents are used in combination, it is usually necessary to add a penetrant, an alkalizer or heat treatment, otherwise it is difficult to achieve a good loading effect for each drug.

[0005] In addition, invention patent US10589003B2 discloses a method for coating or impregnating a non-organic surface with minocycline and rifampicin, dissolving rifampicin and minocycline in dichloromethane, tetrahydrofuran, chloroform, etc. as solvents to prepare an antibiotic-loaded antibacterial catheter, but this method requires curing the coated or impregnated non-organic surface material at a temperature of at least about 40°C, and heating and drying the surface at a temperature of at least 50°C for at least 12 hours, which consumes a lot of energy and has a complicated preparation process.

[0006] Therefore, developing an antibacterial catheter with a high drug loading, good antibacterial effect, and simple preparation method has become a technical problem that needs to be solved urgently. Summary of the invention

[0007] Problem that the invention aims to solve

[0008] In view of the technical problems existing in the prior art, the present invention first provides an antibacterial catheter. The antibacterial catheter of the present invention contains hexafluoroisopropanol in the solvent used in the preparation process. Hexafluoroisopropanol has a good swelling effect on the silicone catheter body, which promotes the loading of the antibacterial agent into the catheter body. Hexafluoroisopropanol is more environmentally friendly and reduces the use of other highly toxic solvents.

[0009] The antibacterial catheter of the present invention contains hexafluoroisopropanol in the solvent used in the preparation process, which can dissolve a variety of antibacterial agents, and is particularly suitable for dissolving clindamycin hydrochloride and minocycline. It can be used as a solvent for the antibacterial agent and a swelling agent for the catheter body at the same time, so that the antibacterial agent solution has a higher concentration. After swelling the catheter body, the catheter body has a higher drug loading amount, uniform drug loading, long-term drug release, and good antibacterial effect.

[0010] Furthermore, the present invention also provides a method for preparing an antibacterial catheter, which is simple and easy to prepare, and the raw materials are easy to obtain, and is suitable for mass production.

[0011] The preparation method of the present invention dissolves drugs in groups, thereby achieving full dissolution of multiple drugs, shortening the preparation time, and reducing mutual influence between drug solutions.

[0012] Solutions for solving problems

[0013] The present invention provides an antibacterial catheter, wherein the antibacterial catheter comprises a catheter body, the material of the catheter body comprises silica gel, and the solvent used in the preparation process of the antibacterial catheter comprises hexafluoroisopropanol, wherein:

[0014] The catheter body is swollen by using the solvent, and the antimicrobial agent is dispersed inside the catheter body.

[0015] Furthermore, the preparation process of the antibacterial catheter includes using the solvent to dissolve the antibacterial agent to obtain an antibacterial agent solution; and using the antibacterial agent solution to swell the catheter body, thereby dispersing the antibacterial agent inside the catheter body.

[0016] Furthermore, the antibacterial agent includes clindamycin hydrochloride and / or minocycline.

[0017] Further, the solvent further comprises dichloromethane and / or tetrahydrofuran, and the antibacterial agent comprises rifampicin and clindamycin hydrochloride, or rifampicin and minocycline;

[0018] Preferably, based on the total mass of the antibacterial catheter being 100%, the drug loading amount of rifampicin is greater than 0.040wt%, and the drug loading amount of clindamycin hydrochloride or minocycline is greater than 0.10wt%.

[0019] Furthermore, the drug sustained release time of the antibacterial catheter is greater than 14 days; the in vitro antibacterial rate of the antibacterial catheter within 7 days is greater than 95%; and / or,

[0020] The antibacterial catheter is a drainage catheter, preferably a drainage catheter used for cerebrospinal fluid drainage.

[0021] Furthermore, the tip of the antibacterial catheter has an asymmetric drainage hole, and the maximum distance between two points passing through the center on the drainage hole contour line is the long diameter, and the minimum distance between two points passing through the center on the drainage hole contour line is the short diameter;

[0022] Preferably, the antibacterial catheter has a first drainage hole and a second drainage hole, the major diameter of the first drainage hole is greater than the major diameter of the second drainage hole; and / or the number of the first drainage holes is less than the number of the second drainage holes;

[0023] More preferably, the long diameter of the first drainage hole is 4.0 mm-5.5 mm, and the short diameter is 1.0 mm-2.5 mm; the long diameter of the second drainage hole is 2.0 mm-2.5 mm, and the short diameter is 1.0 mm-2.5 mm.

[0024] The present invention also proposes a method for preparing the antibacterial catheter according to the present invention, wherein the preparation method comprises immersing the catheter body in an antibacterial agent solution to swell the catheter body, so that the antibacterial agent is dispersed inside the catheter body; wherein the antibacterial agent is dissolved in a solvent including hexafluoroisopropanol to obtain the antibacterial agent solution.

[0025] Furthermore, the antibacterial agent includes clindamycin hydrochloride and / or minocycline, and the method for preparing the antibacterial catheter includes dissolving the clindamycin hydrochloride and / or the minocycline in the solvent to obtain the antibacterial agent solution, and then immersing the catheter body in the antibacterial agent solution to disperse the antibacterial agent inside the catheter body.

[0026] Furthermore, the solvent used in the preparation process of the antibacterial catheter also includes dichloromethane and / or tetrahydrofuran;

[0027] The antibacterial agents include rifampicin and clindamycin hydrochloride, or rifampicin and minocycline; and,

[0028] The preparation method comprises the following steps:

[0029] Dissolving a first antimicrobial agent in a first solvent to obtain a first antimicrobial agent solution; wherein the first antimicrobial agent includes rifampicin, and the first solvent includes dichloromethane and / or tetrahydrofuran;

[0030] Dissolving a second antibacterial agent in a second solvent to obtain a second antibacterial agent solution; wherein the second antibacterial agent includes clindamycin hydrochloride and / or minocycline, and the second solvent includes hexafluoroisopropanol;

[0031] Mixing the first antimicrobial agent solution and the second antimicrobial agent solution uniformly to obtain the antimicrobial agent mixed solution;

[0032] The catheter body is immersed in the antibacterial agent mixed solution, then taken out, and the first solvent and the second solvent are removed to obtain an antibacterial catheter.

[0033] Further, in the antimicrobial agent mixed solution, relative to the total volume of the first solvent and the second solvent, the mass-volume concentration of the first antimicrobial agent is 0.002 g / mL-2 g / mL, preferably 0.01 g / mL-1.0 g / mL, and the mass-volume concentration of the second antimicrobial agent is 0.002 g / mL-2 g / mL, preferably 0.01 g / mL-1.0 g / mL; and / or,

[0034] The volume ratio of the first solvent to the second solvent is 1:(0.05-30), preferably 1:(0.1-10).

[0035] Effects of the Invention

[0036] The catheter body of the antibacterial catheter of the present invention is swollen by a solvent, and the solvent used contains hexafluoroisopropanol, which has a good swelling effect on the catheter body containing silica gel. Therefore, when the antibacterial agent is dispersed in the catheter body, the present invention does not need to add additional alkalizing agents, penetrants or drug solubilizers, etc., and does not need to use subsequent treatments such as heating or high-pressure sterilization.

[0037] Furthermore, when one or more other solvents are mixed with hexafluoroisopropanol to swell the catheter body, the swelling degree of the catheter body can be adjusted and enhanced.

[0038] Furthermore, hexafluoroisopropanol can dissolve a variety of antibacterial agents, especially clindamycin hydrochloride and minocycline, and has good solubility. Therefore, hexafluoroisopropanol can be used as a solvent for antibacterial agents and a swelling agent for the catheter body at the same time, so that the antibacterial catheter has good drug loading effect and sustained release effect.

[0039] Furthermore, the antibacterial catheter of the present invention can be loaded with more than two antibacterial drugs, which can enhance the antibacterial synergy of the catheter, thereby improving the broad-spectrum antibacterial property of the catheter against a variety of microorganisms. The antibacterial catheter of the present invention has a high drug loading capacity for the loaded multiple drugs and has a good antibacterial effect.

[0040] Furthermore, the preparation method of the antibacterial catheter of the present invention is simple and easy, the raw materials are easy to obtain, and it is suitable for mass production. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 The swelling effect diagram of the antibacterial catheter of Example 3 is shown;

[0042] Figure 2 The swelling effect diagram of the antibacterial catheter of Comparative Example 1 is shown;

[0043] Figure 3 is a drug release curve of rifampicin in the antibacterial catheter of Example 3;

[0044] Figure 4 is a drug release curve of clindamycin hydrochloride in the antibacterial catheter of Example 3;

[0045] Figure 5 The schematic diagram of the structure of the antibacterial catheter of the present invention is shown; wherein the left figure is a front view of the antibacterial catheter, and the right figure is a rear view of the antibacterial catheter. DETAILED DESCRIPTION

[0046] Various exemplary embodiments, features and aspects of the present invention will be described in detail below. The word "exemplary" used here means "used as an example, embodiment or illustrative". Any embodiment described here as "exemplary" is not necessarily interpreted as being superior or better than other embodiments.

[0047] In addition, in order to better illustrate the present invention, numerous specific details are provided in the following specific embodiments. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In other examples, methods, means, equipment and steps well known to those skilled in the art are not described in detail in order to highlight the subject matter of the present invention.

[0048] Unless otherwise stated, the units used in this specification are all international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0049] In this specification, the word "may" means both performing a certain process and not performing a certain process.

[0050] In this specification, the references to "some specific / preferred embodiments", "other specific / preferred embodiments", "embodiments", etc., mean that the specific elements (e.g., features, structures, properties and / or characteristics) described in connection with the embodiments are included in at least one embodiment described herein, and may or may not exist in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any suitable manner.

[0051] In this specification, the numerical range expressed using "numerical value A - numerical value B" means a range including the endpoint numerical values ​​A and B.

[0052] In this specification, "mass-volume concentration" means the ratio of the mass of a solute to the volume of a solvent.

[0053] In this specification, the temperature of "room temperature" or "normal temperature" can be 15-30°C, for example: 20-25°C.

[0054] <First aspect>

[0055] A first aspect of the present invention provides an antibacterial catheter, comprising a catheter body, wherein the material of the catheter body comprises silica gel, and the solvent used in the preparation process of the antibacterial catheter comprises hexafluoroisopropanol, wherein:

[0056] The catheter body is swollen by using the solvent, and the antimicrobial agent is dispersed inside the catheter body.

[0057] The antibacterial catheter of the present invention comprises a catheter body, wherein the catheter body has an inlet (such as a drainage hole) and an outlet, wherein the inlet and the outlet are connected through the catheter body to form a cavity structure. The material of the catheter body comprises silica gel.

[0058] Specifically, Figure 5 As shown, the tip of the antibacterial catheter has an asymmetric drainage hole, and the maximum distance between two points passing through the center on the drainage hole contour line is the long diameter, and the minimum distance between two points passing through the center on the drainage hole contour line is the short diameter.

[0059] Preferably, the antibacterial catheter has a first drainage hole and a second drainage hole. The long diameter of the first drainage hole is greater than the long diameter of the second drainage hole; and / or the number of the first drainage holes is less than the number of the second drainage holes. More preferably, the long diameter of the first drainage hole is 4.0mm-5.5mm, and the short diameter is 1.0mm-2.5mm; the long diameter of the second drainage hole is 2.0mm-2.5mm, and the short diameter is 1.0mm-2.5mm.

[0060] The present invention can prevent a large piece of drainage material from blocking the catheter by setting the first drainage hole; can prevent the puncture needle from falling out during the puncture process by setting the second drainage hole, and the small hole is suitable for drainage after puncture.

[0061] In the present invention, the antibacterial catheter also has a ring-printed scale line that surrounds the entire axial direction of the antibacterial catheter, which is convenient for observing the insertion depth of the catheter from different angles. Preferably, the distance between adjacent ring-printed scale lines is 1 cm or 2 cm, and the middle distance between adjacent ring-printed scale lines is marked with dot scales. Furthermore, numbers are printed on at least two sides for easy reading.

[0062] In the present invention, the solvent used in the preparation process of the antibacterial catheter includes hexafluoroisopropanol. The inventor of the present invention found that hexafluoroisopropanol has a good swelling effect on the catheter body. The antibacterial catheter of the present invention uses hexafluoroisopropanol as a solvent, which expands the use range of conventional solvents.

[0063] Hexafluoroisopropanol can dissolve a variety of antimicrobial agents and has a good swelling effect on the catheter body. Therefore, the present invention does not need to add additional alkalizing agents, penetrants or drug solubilizers (such as NaOH) when dispersing the antimicrobial agent in the catheter body, nor does it need to use subsequent treatments such as heating or high-pressure sterilization.

[0064] In the present invention, hexafluoroisopropanol can be used as a solvent for a variety of antimicrobial agents. While dissolving the antimicrobial agents, it penetrates and "swells" the entire catheter body, causing the internal pores of the catheter body to open, and the antimicrobial agents can enter these pores, thereby achieving uniform dispersion of the antimicrobial agents in the catheter body. Therefore, hexafluoroisopropanol can also achieve better loading and release effects for a variety of antimicrobial agents in the drug-containing drainage catheter of the present invention.

[0065] In the present invention, the catheter body is swollen by using the solvent, and the antibacterial agent is allowed to penetrate into the catheter body. Specifically, the preparation process of the antibacterial catheter includes using the solvent to dissolve the antibacterial agent to obtain an antibacterial agent solution; and using the antibacterial agent solution to swell the catheter body, so that the antibacterial agent is dispersed inside the catheter body. Furthermore, the antibacterial catheter of the present invention can be loaded with more than two antibacterial drugs at the same time, which can enhance the antibacterial synergy of the catheter, thereby improving the broad-spectrum antibacterial property of the catheter against a variety of microorganisms. The antibacterial catheter of the present invention also has a high drug loading capacity and a good antibacterial effect.

[0066] In some specific embodiments, the antibacterial agent includes clindamycin hydrochloride and / or minocycline. Among them, minocycline is a tetracycline antibiotic with a wide antibacterial spectrum and can effectively fight against a variety of bacteria, including gram-positive and gram-negative bacteria. Clindamycin hydrochloride mainly works by inhibiting the synthesis of bacterial proteins, especially against gram-positive bacteria (such as Staphylococcus aureus, Streptococcus, etc.) and some anaerobic bacteria.

[0067] When the antibacterial agent includes clindamycin hydrochloride and / or minocycline, the preparation process of the antibacterial catheter includes dissolving the clindamycin hydrochloride and / or minocycline in the solvent to obtain the antibacterial agent solution, and then immersing the catheter body in the antibacterial agent solution to disperse the antibacterial agent inside the catheter body.

[0068] In some specific embodiments, the solvent used in the preparation process of the antibacterial catheter further includes dichloromethane and / or tetrahydrofuran. The inventors of the present invention have found that when dichloromethane and / or tetrahydrofuran are mixed with hexafluoroisopropanol and acted on the catheter body, the swelling degree of the catheter body can be adjusted and enhanced, and the drug loading can be further increased.

[0069] In some specific embodiments, the antibacterial agent includes rifampicin and clindamycin hydrochloride, or the antibacterial agent includes rifampicin and minocycline. The present invention can produce a synergistic effect by using rifampicin and clindamycin hydrochloride or rifampicin and minocycline combination, and can more effectively inhibit or kill bacteria. Rifampicin is a rifamycin antibiotic, which also has a broad-spectrum antibacterial effect, especially effective against Mycobacterium tuberculosis and other difficult-to-treat bacteria.

[0070] In some specific embodiments, based on the total mass of the antibacterial catheter as 100%, the drug loading of rifampicin is 0.040wt% or more, for example: 0.040wt%-0.1wt%; the drug loading of clindamycin hydrochloride or minocycline is 0.10wt% or more, for example: 0.10wt%-0.2wt%. The antibacterial catheter of the present invention can load more than two antibacterial drugs at the same time, which can enhance the antibacterial synergy of the catheter, thereby improving the broad-spectrum antibacterial property of the catheter against multiple microorganisms.

[0071] The antibacterial catheter of the present invention has a long drug release time and excellent antibacterial effect. Specifically, the drug release time of the antibacterial catheter is greater than 14 days; and the in vitro antibacterial rate of the antibacterial catheter within 7 days is greater than 95%.

[0072] The antimicrobial catheter of the present invention is suitable for preparing various medical implants, including but not limited to drainage catheters, vascular catheters, dialysis catheters, long-term tunneled central venous catheters, peripheral venous catheters, short-term central venous catheters, arterial catheters, Swan-Ganz pulmonary artery catheters, urinary catheters, long-term urinary devices, tissue-integrated urinary devices, penile prostheses, vascular transplants, vascular catheter ports, wound drainage tubes, hydrocephalus shunts, peritoneal dialysis catheters, pacemaker capsules, artificial urinary sphincters, small or temporary joint replacements, urinary dilators or heart valves, etc., and is particularly suitable for drainage catheters, especially cerebrospinal fluid external drainage catheters.

[0073] <Second Aspect>

[0074] The second aspect of the present invention provides a method for preparing the antibacterial catheter according to the first aspect of the present invention, the preparation method comprising immersing the catheter body in an antibacterial agent solution to disperse the antibacterial agent inside the catheter body; wherein the antibacterial agent is dissolved in a solvent including hexafluoroisopropanol to obtain the antibacterial agent solution.

[0075] The present invention uses a solvent to penetrate and "swell" the entire catheter body, so that the internal channels of the catheter body are opened. At the same time, the antibacterial agent can enter these channels, so that the antibacterial agent is evenly dispersed in the catheter body.

[0076] The preparation method of the antibacterial catheter of the present invention is simple. During the swelling and impregnation process of the catheter body, there is no need to add additional alkalizing agents, penetrants or drug solubilizers (such as NaOH), and there is no need to use subsequent treatments such as heating or high-pressure sterilization. After the solvent is naturally evaporated and then dried, a high load of multiple drugs on the catheter body and long-term antibacterial effects can be achieved.

[0077] In some specific embodiments, the antibacterial agent includes clindamycin hydrochloride and / or minocycline, and the method for preparing the antibacterial catheter includes dissolving the clindamycin hydrochloride and / or the minocycline in the solvent including hexafluoroisopropanol to obtain the antibacterial agent solution, and then immersing the catheter body in the antibacterial agent solution to disperse the antibacterial agent inside the catheter body.

[0078] In some specific embodiments, the solvent used in the preparation process of the antibacterial catheter further includes dichloromethane and / or tetrahydrofuran; the antibacterial agent includes rifampicin and clindamycin hydrochloride, or rifampicin and minocycline. When the combination of the solvent and the antibacterial agent of this embodiment is used, rifampicin and clindamycin hydrochloride, or rifampicin and minocycline, can have a good loading effect.

[0079] In some specific embodiments, in order to shorten the preparation time of the antibacterial agent mixed solution, reduce the risk of drug degradation and crystallization, and improve the drug loading performance of the antibacterial catheter, thereby improving the antibacterial effect of the catheter, the preparation method includes the following steps:

[0080] Dissolving a first antimicrobial agent in a first solvent to obtain a first antimicrobial agent solution; wherein the first antimicrobial agent includes rifampicin, and the first solvent includes dichloromethane and / or tetrahydrofuran;

[0081] Dissolving a second antibacterial agent in a second solvent to obtain a second antibacterial agent solution; wherein the second antibacterial agent includes clindamycin hydrochloride and / or minocycline, and the second solvent includes hexafluoroisopropanol;

[0082] Mixing the first antimicrobial agent solution and the second antimicrobial agent solution uniformly to obtain the antimicrobial agent mixed solution;

[0083] The catheter body is immersed in the antibacterial agent mixed solution, then taken out, and the first solvent and the second solvent are removed to obtain an antibacterial catheter.

[0084] The present invention can quickly achieve complete dissolution of the first antibacterial agent and the second antibacterial agent by dissolving the first antibacterial agent and the second antibacterial agent in the first solvent and the second solvent respectively and then mixing them, shortening the preparation time of the mixed solution of the first antibacterial agent and the second antibacterial agent, reducing the risks of drug degradation and crystallization, thereby improving the drug loading effect and drug release effect of the catheter.

[0085] In some specific embodiments, in the antimicrobial agent mixed solution, relative to the total volume of the first solvent and the second solvent, the mass-volume concentration of the first antimicrobial agent can be 0.002g / mL-2g / mL, preferably 0.01g / mL-1.0g / mL, and the mass-volume concentration of the second antimicrobial agent can be 0.002g / mL-2g / mL, preferably 0.01g / mL-1.0g / mL.

[0086] Further, in the present invention, the volume ratio of the first solvent to the second solvent may be 1:(0.05-30), preferably 1:(0.1-10).

[0087] Furthermore, the present invention obtains an antibacterial catheter by immersing the catheter body in the antibacterial agent mixed solution, taking it out, and removing the first solvent and the second solvent. The present invention does not specifically limit the immersion time, which can be 0.5h-1h. Specifically, the catheter body is immersed in the antibacterial agent mixed solution, sealed and protected from light, and taken out after immersion for 0.5h-1h at room temperature.

[0088] Furthermore, the present invention does not specifically limit the method for removing the solvent, and the solvent can generally be volatilized under natural conditions, for example, volatilizing the solvent in a fume hood at room temperature.

[0089] Furthermore, the preparation method of the present invention further comprises the step of post-processing the antibacterial catheter; preferably, the post-processing comprises washing and then drying the antibacterial catheter. For drying, in order to prevent the function of the antibacterial catheter from being damaged, the present invention preferably dries it at room temperature.

[0090] Example

[0091] The embodiments of the present invention will be described in detail below in conjunction with the examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. If no specific conditions are specified in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0092] Example 1

[0093] S1: Preparation of antimicrobial solution

[0094] (1) Weigh 1.5 g of clindamycin hydrochloride, dissolve it in 1.5 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a clindamycin hydrochloride antibacterial agent solution with a mass-volume concentration of 1.0 g / mL.

[0095] S2: Preparation of antimicrobial catheter

[0096] A 1 cm long silicone catheter was immersed in the above antibacterial solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0097] Example 2

[0098] S1: Preparation of antimicrobial solution

[0099] (1) Weigh 0.5 g of rifampicin, dissolve it in 0.5 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a rifampicin antibacterial agent solution with a mass-volume concentration of 1.0 g / mL.

[0100] (2) Weigh 1.0 g of clindamycin hydrochloride, dissolve it in 1.0 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a clindamycin hydrochloride antibacterial agent solution with a mass-volume concentration of 1.0 g / mL.

[0101] (3) The rifampicin antibacterial solution and the clindamycin hydrochloride antibacterial solution are uniformly mixed to prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, the mass-volume concentration of rifampicin relative to the total volume of hexafluoroisopropanol is 0.33 g / mL, and the mass-volume concentration of clindamycin hydrochloride is 0.67 g / mL.

[0102] S2: Preparation of antimicrobial catheter

[0103] A 1 cm long silicone catheter was immersed in the above antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0104] Example 3

[0105] S1: Preparation of antimicrobial solution:

[0106] (1) Weigh 0.008 g of rifampicin, dissolve it in 0.5 mL of dichloromethane, and stir to dissolve, thereby preparing a rifampicin antibacterial solution with a mass volume concentration of 0.016 g / mL.

[0107] (2) Weigh 0.012 g of clindamycin hydrochloride, dissolve it in 1.0 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a clindamycin hydrochloride antibacterial agent solution with a mass-volume concentration of 0.012 g / mL.

[0108] (3) The rifampicin antibacterial solution and the clindamycin hydrochloride antibacterial solution are uniformly mixed to prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, relative to the total volume of dichloromethane and hexafluoroisopropanol, the mass-volume concentration of rifampicin is 0.0053 g / mL, and the mass-volume concentration of clindamycin hydrochloride is 0.0080 g / mL; and the volume ratio of dichloromethane to hexafluoroisopropanol is 1:2.

[0109] S2: Preparation of antimicrobial catheter:

[0110] A 1 cm long silicone catheter was immersed in the above antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0111] Example 4

[0112] S1: Preparation of antimicrobial solution:

[0113] (1) Weigh 0.008 g of rifampicin, dissolve it in 0.5 mL of tetrahydrofuran, and stir to dissolve it to prepare a rifampicin antibacterial agent solution with a mass-volume concentration of 0.016 g / mL.

[0114] (2) Weigh 0.012 g of clindamycin hydrochloride, dissolve it in 1.0 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a clindamycin hydrochloride antibacterial agent solution with a mass-volume concentration of 0.012 g / mL.

[0115] (3) The rifampicin antibacterial solution and the clindamycin hydrochloride antibacterial solution are uniformly mixed to prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, relative to the total volume of tetrahydrofuran and hexafluoroisopropanol, the mass-volume concentration of rifampicin is 0.0053 g / mL, and the mass-volume concentration of clindamycin hydrochloride is 0.0080 g / mL; and the volume ratio of tetrahydrofuran to hexafluoroisopropanol is 1:2.

[0116] S2: Preparation of antimicrobial catheter:

[0117] A 1 cm long silicone catheter was immersed in the above antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0118] Example 5

[0119] S1: Preparation of antimicrobial solution

[0120] (1) Weigh 0.008 g of rifampicin, dissolve it in 0.8 mL of dichloromethane, and stir to dissolve it to prepare a rifampicin antibacterial agent solution with a mass-volume concentration of 0.01 g / mL.

[0121] (2) Weigh 0.012 g of clindamycin hydrochloride, dissolve it in 0.7 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a clindamycin hydrochloride antibacterial agent solution with a mass-volume concentration of 0.017 g / mL.

[0122] (3) The rifampicin antibacterial solution and the clindamycin hydrochloride antibacterial solution are uniformly mixed to prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, relative to the total volume of dichloromethane and hexafluoroisopropanol, the mass-volume concentration of rifampicin is 0.0053 g / mL, and the mass-volume concentration of clindamycin hydrochloride is 0.0080 g / mL; and the volume ratio of dichloromethane to hexafluoroisopropanol is 1:0.875.

[0123] S2: Preparation of antimicrobial catheter

[0124] A 1 cm long silicone catheter was immersed in the above antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0125] Example 6

[0126] S1: Preparation of antimicrobial solution

[0127] (1) Weigh 0.012 g of rifampicin, dissolve it in 0.5 mL of tetrahydrofuran, and stir to dissolve, thereby preparing a rifampicin antibacterial agent solution with a mass-volume concentration of 0.024 g / mL.

[0128] (2) Weigh 0.016 g of clindamycin hydrochloride, dissolve it in 1.0 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a clindamycin hydrochloride antibacterial agent solution with a mass-volume concentration of 0.016 g / mL.

[0129] (3) The rifampicin antibacterial solution and the clindamycin hydrochloride antibacterial solution are uniformly mixed to prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, relative to the total volume of tetrahydrofuran and hexafluoroisopropanol, the mass-volume concentration of rifampicin is 0.008 g / mL, and the mass-volume concentration of clindamycin hydrochloride is 0.0107 g / mL; and the volume ratio of tetrahydrofuran to hexafluoroisopropanol is 1:2.

[0130] S2: Preparation of antimicrobial catheter

[0131] A 1 cm long silicone catheter was immersed in the above antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0132] Example 7

[0133] S1: Preparation of antimicrobial solution

[0134] (1) Weigh 0.008 g of rifampicin, dissolve it in 0.5 mL of dichloromethane, and stir to dissolve it to prepare a rifampicin antibacterial agent solution with a mass-volume concentration of 0.016 g / mL.

[0135] (2) Weigh 0.012 g of minocycline, dissolve it in 1.0 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a minocycline antibacterial agent solution with a mass-volume concentration of 0.012 g / mL.

[0136] (3) The rifampicin antibacterial solution and the minocycline antibacterial solution are uniformly mixed to prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, relative to the total volume of dichloromethane and hexafluoroisopropanol, the mass-volume concentration of rifampicin is 0.0053 g / mL, and the mass-volume concentration of minocycline is 0.0080 g / mL; and the volume ratio of dichloromethane to hexafluoroisopropanol is 1:2.

[0137] S2: Preparation of antimicrobial catheter

[0138] A 1 cm long silicone catheter was immersed in the above antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0139] Example 8

[0140] S1: Preparation of antimicrobial solution

[0141] (1) Weigh 0.008 g of rifampicin, dissolve it in 0.5 mL of tetrahydrofuran, and stir to dissolve, thereby preparing a rifampicin antibacterial solution with a mass-volume concentration of 0.016 g / mL.

[0142] (2) Weigh 0.012 g of minocycline, dissolve it in 1.0 mL of hexafluoroisopropanol, and stir to dissolve, thereby preparing a minocycline antibacterial agent solution with a mass-volume concentration of 0.012 g / mL.

[0143] (3) The rifampicin antibacterial solution and the minocycline antibacterial solution are uniformly mixed to prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, relative to the total volume of tetrahydrofuran and hexafluoroisopropanol, the mass-volume concentration of rifampicin is 0.0053 g / mL, and the mass-volume concentration of minocycline is 0.0080 g / mL; and the volume ratio of tetrahydrofuran to hexafluoroisopropanol is 1:2.

[0144] S2: Preparation of antimicrobial catheter

[0145] A 1 cm long silicone catheter was immersed in the above antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0146] Comparative Example 1

[0147] S1: Preparation of antimicrobial solution

[0148] Weigh 0.008 g of rifampicin and 0.012 g of clindamycin hydrochloride, add them to 1.5 mL of dichloromethane, stir to dissolve, and prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, the mass-volume concentration of rifampicin relative to the volume of dichloromethane is 0.0053 g / mL, and clindamycin hydrochloride forms a precipitate.

[0149] S2: Preparation of antimicrobial catheter

[0150] A 1 cm long silicone catheter was immersed in the antibacterial agent mixed solution from which the precipitate was removed, sealed and protected from light, and after being immersed at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter.

[0151] Comparative Example 2

[0152] S1: Preparation of antimicrobial solution

[0153] Weigh 0.008 g of rifampicin and 0.012 g of clindamycin hydrochloride, add them to 1.5 mL of tetrahydrofuran, stir to dissolve, and prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, the mass-volume concentration of rifampicin relative to the solvent volume is 0.0053 g / mL, and clindamycin hydrochloride forms a precipitate.

[0154] S2: Preparation of antimicrobial catheter

[0155] A 1 cm long silicone catheter was immersed in the antibacterial agent mixed solution from which the precipitate was removed, sealed and protected from light, and after being immersed at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter.

[0156] Comparative Example 3

[0157] S1: Preparation of antimicrobial solution

[0158] Weigh 0.008 g of rifampicin and 0.012 g of clindamycin hydrochloride, add them to 1.5 mL of methanol, stir to dissolve, and prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, relative to the volume of the solvent, the mass-volume concentration of rifampicin is 0.0053 g / mL, and the mass-volume concentration of clindamycin hydrochloride is 0.008 g / mL.

[0159] S2: Preparation of antimicrobial catheter

[0160] A 1 cm long silicone catheter was immersed in the antibacterial agent mixed solution from which the precipitate was removed, sealed and protected from light, and after being immersed at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter.

[0161] Comparative Example 4

[0162] S1: Preparation of antimicrobial solution

[0163] (1) Weigh 0.008 g of rifampicin, dissolve it in 0.5 mL of acetonitrile, and stir to dissolve to prepare a rifampicin antibacterial agent solution with a mass-volume concentration of 0.016 g / mL.

[0164] (2) Weigh 0.012 g of clindamycin hydrochloride, add it to 1.0 mL of methanol, stir to dissolve, and prepare a clindamycin hydrochloride antibacterial agent solution with a mass-volume concentration of 0.008 g / mL.

[0165] (3) The rifampicin antibacterial solution and the clindamycin hydrochloride antibacterial solution from which the precipitate has been removed are mixed uniformly to prepare an antibacterial mixed solution; wherein in the antibacterial mixed solution, the mass-volume concentration of rifampicin relative to the total volume of methanol and acetonitrile is 0.0053 g / mL, and the mass-volume concentration of clindamycin hydrochloride is 0.008 g / mL.

[0166] S2: Preparation of antimicrobial catheter

[0167] A 1 cm long silicone catheter was immersed in the above antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 hour, the silicone catheter was taken out and the excess solvent was evaporated under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0168] Performance Testing

[0169] 1. Swelling performance test

[0170] The volume swelling degree was used to evaluate the swelling performance of the antibacterial catheters of Examples 1-8 and Comparative Examples 1-4 during the preparation process. A silicone catheter of a certain length was cut and immersed in the corresponding solvents of Examples 1-8 and Comparative Examples 1-4 for a certain period of time. After the swelling equilibrium was reached, the volume swelling degree was calculated. The volume swelling degree was calculated as follows: (volume of the antibacterial catheter after swelling equilibrium - volume of the antibacterial catheter before swelling) / volume of the antibacterial catheter before swelling * 100%, and the results are shown in Table 1.

[0171] Table 1 Volume swelling during the preparation of antibacterial catheters

[0172] Example / Comparative Example Volume swelling (%) Example 1 47.81 Example 2 49.76 Example 3 108.47 Example 4 98.37 Example 5 110.32 Example 6 99.29 Example 7 105.65 Example 8 101.27 Comparative Example 1 119.52 Comparative Example 2 151.24 Comparative Example 3 15.01 Comparative Example 4 5.51

[0173] It can be seen from Table 1 that, compared with Comparative Examples 3 and 4, the antibacterial catheter of the present invention has a higher volume swelling degree after swelling equilibrium, and hexafluoroisopropanol has a better swelling effect on the catheter body, which is beneficial for the antibacterial catheter to load more antibacterial solution.

[0174] 2. Drug loading

[0175] The antibacterial catheters of Examples 1-8 and Comparative Examples 1-4 were cut to a certain length, immersed in chloroform for a certain period of time, the chloroform was completely volatilized to obtain drug particles, the drugs were dissolved, the drug concentration was measured using a liquid chromatograph, and the content of each drug in the antibacterial catheter (i.e., drug loading) was calculated. The calculation formula for drug loading is: drug loading = (mass of a single drug / mass of drug-loaded silica gel catheter) × 100%. The results are shown in Tables 2 and 3 below. Table 2 shows the drug loading of the drugs in the antibacterial catheters of Examples 1-8, and Table 3 shows the drug loading of the drugs in the antibacterial catheters of Comparative Examples 1-4.

[0176] Table 2 Drug loading of each drug in the antibacterial catheter of Examples 1-8

[0177] Example Rifampicin (wt%) Clindamycin hydrochloride (wt%) Minocycline (wt%) 1 / 0.0638±0.0004 / 2 0.0372±0.00003 0.0543±0.0004 / 3 0.0411±0.00001 0.108±0.0004 / 4 0.0402±0.00002 0.107±0.0001 / 5 0.0418±0.00002 0.123±0.0001 / 6 0.0415±0.00001 0.113±0.0012 / 7 0.0414±0.00002 / 0.135±0.0011 8 0.0405±0.00002 / 0.111±0.0005

[0178] Table 3 Drug loading of each drug in the antibacterial catheter of Comparative Examples 1-4

[0179] Comparative Example Rifampicin (wt%) Clindamycin hydrochloride (wt%) 1 0.0353±0.00005 ND 2 0.0386±0.00005 ND 3 0.0008±0.000002 0.0003±0.000002 4 ND ND

[0180] It can be seen from Table 2 and Table 3 that the drug loading of rifampicin in Examples 1-8 is higher than that in Comparative Examples 1-4. In addition, it can be seen from Table 2 and Table 3 that in Examples 3-8, the drug loading of rifampicin can reach greater than 0.04wt%, and the drug loading of clindamycin hydrochloride or minocycline can reach greater than 0.10wt%. In Example 2, the drug loading of rifampicin can also reach greater than 0.03wt%, and the drug loading of clindamycin hydrochloride can reach greater than 0.05wt%. In Example 1, the drug loading of clindamycin hydrochloride can reach greater than 0.05wt%.

[0181] In Comparative Examples 1-2, although the swelling degree of the antibacterial catheters of Comparative Examples 1 and 2 is high, since clindamycin hydrochloride is not dissolved, the drug loading of clindamycin hydrochloride cannot be detected. In Comparative Example 3, methanol has a low swelling degree for the catheter. Even if it can dissolve a certain amount of clindamycin hydrochloride, the drug loading of rifampicin and clindamycin hydrochloride is very small. In Comparative Example 4, the conventional composite solvent hardly swells the antibacterial catheter, and the antibacterial agent mixed solution can hardly penetrate into the interior of the catheter. Therefore, the drug loading of rifampicin and clindamycin hydrochloride cannot be detected. It can be seen that the solvent including hexafluoroisopropanol used in the present invention can swell the catheter well, and at the same time has good solubility of the antibacterial agent, so that the antibacterial catheter has a better drug loading effect.

[0182] In addition, from Figure 1 and Figure 2 It can be seen from the apparent color depth that the drug loading amount of the antibacterial catheter of Example 3 is much higher than that of the antibacterial catheter of Comparative Example 1.

[0183] 3. Antimicrobial activity

[0184] Cut a certain length of the antibacterial catheter prepared in Example 3, place it in a certain concentration of Staphylococcus aureus suspension, and then incubate it at 37°C. The Staphylococcus aureus suspension is used as a blank control group. Take out the drainage tube every other day and immerse it in a newly prepared Staphylococcus aureus suspension test tube. At the same time, replace the blank control group with a new bacterial suspension tube. Take three samples at two time points of incubation for 1 day and 7 days, take the bacterial suspension at the end of incubation, dilute it, count the number of colonies by the coating plate method, and compare it with the blank control group to calculate the antibacterial rate. The calculation formula of the antibacterial rate is: Antibacterial rate = (number of colonies in the blank control group - number of colonies in the sample group) / number of colonies in the blank control group × 100%. The results are shown in Table 4.

[0185] Table 4 In vitro antibacterial rate of the antibacterial catheter of Example 3

[0186]

[0187] As can be seen from Table 4, the present invention adopts a solvent-swollen silicone catheter including hexafluoroisopropanol to load at least two antibacterial drugs, and a high drug loading of multiple antibacterial agents can be achieved in a short time, and the prepared antibacterial catheter has low-concentration sustained release and long-acting antibacterial effect, thereby enhancing the antibacterial synergy of the catheter and improving the broad-spectrum antibacterial property of the catheter against multiple microorganisms.

[0188] 4. Sustained release time

[0189] The antibacterial catheter of Example 3 was cut into a certain length, immersed in a PBS solution, and placed in a shaker at 37° C. for continuous release. The drug solution was taken at different time points, and the drug concentration was measured using a liquid chromatograph to draw a drug release concentration-time curve.

[0190] The release curves of rifampicin and clindamycin hydrochloride in the antibacterial catheter prepared in Example 3 are as follows: Figure 3 and Figure 4 As shown in the figure, it can be seen that rifampicin and clindamycin hydrochloride in the antibacterial catheter can be slowly released at low concentrations for up to 350 hours, which can prevent bacteria from colonizing on the surface of the antibacterial catheter. In addition, it can be seen from the in vitro antibacterial rate results in Table 4 that when the new bacterial solution is replaced every day, the antibacterial rate of the antibacterial catheter can still be maintained at more than 95% after 7 days.

[0191] It should be noted that, although the technical solution of the present invention is introduced with specific examples, those skilled in the art will appreciate that the present invention should not be limited thereto.

[0192] The embodiments of the present invention have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. An antimicrobial catheter, It is characterized in that The antibacterial catheter comprises a catheter body, the material of the catheter body comprises silica gel, and the solvent used in the preparation process of the antibacterial catheter comprises hexafluoroisopropanol, wherein: The catheter body is swollen by using the solvent, and the antimicrobial agent is dispersed inside the catheter body.

2. The antimicrobial catheter according to claim 1, It is characterized in that The preparation process of the antibacterial catheter comprises using the solvent to dissolve the antibacterial agent to obtain an antibacterial agent solution; and using the antibacterial agent solution to swell the catheter body, thereby dispersing the antibacterial agent inside the catheter body.

3. The antimicrobial catheter according to claim 1 or 2, It is characterized in that The antibacterial agents include clindamycin hydrochloride and / or minocycline.

4. The antimicrobial catheter according to any one of claims 1 to 3, It is characterized in that The solvent further comprises dichloromethane and / or tetrahydrofuran, and the antibacterial agent comprises rifampicin and clindamycin hydrochloride, or rifampicin and minocycline; Preferably, based on the total mass of the antibacterial catheter being 100%, the drug loading amount of rifampicin is greater than 0.040wt%, and the drug loading amount of clindamycin hydrochloride or minocycline is greater than 0.10wt%.

5. The antimicrobial catheter according to any one of claims 1 to 4, It is characterized in that The drug sustained release time of the antibacterial catheter is greater than 14 days; the in vitro antibacterial rate of the antibacterial catheter within 7 days is greater than 95%; and / or, The antibacterial catheter is a drainage catheter, preferably a drainage catheter used for cerebrospinal fluid drainage.

6. The antimicrobial catheter according to any one of claims 1 to 5, It is characterized in that The tip of the antibacterial catheter has an asymmetric drainage hole, and the maximum distance between two points passing through the center on the drainage hole contour line is the long diameter, and the minimum distance between two points passing through the center on the drainage hole contour line is the short diameter; Preferably, the antibacterial catheter has a first drainage hole and a second drainage hole, the major diameter of the first drainage hole is greater than the major diameter of the second drainage hole; and / or the number of the first drainage holes is less than the number of the second drainage holes; More preferably, the long diameter of the first drainage hole is 4.0 mm-5.5 mm, and the short diameter is 1.0 mm-2.5 mm; the long diameter of the second drainage hole is 2.0 mm-2.5 mm, and the short diameter is 1.0 mm-2.5 mm.

7. A method for preparing an antibacterial catheter according to any one of claims 1 to 6, It is characterized in that The preparation method comprises immersing the catheter body in an antibacterial agent solution to swell the catheter body, so that the antibacterial agent is dispersed inside the catheter body; wherein the antibacterial agent is dissolved in a solvent including hexafluoroisopropanol to obtain the antibacterial agent solution.

8. The preparation method according to claim 7, It is characterized in that The antibacterial agent includes clindamycin hydrochloride and / or minocycline. The preparation method of the antibacterial catheter includes dissolving the clindamycin hydrochloride and / or minocycline in the solvent to obtain the antibacterial agent solution, and then immersing the catheter body in the antibacterial agent solution to disperse the antibacterial agent inside the catheter body.

9. The preparation method according to claim 8, It is characterized in that The solvent used in the preparation process of the antibacterial catheter also includes dichloromethane and / or tetrahydrofuran; The antibacterial agents include rifampicin and clindamycin hydrochloride, or rifampicin and minocycline; and, The preparation method comprises the following steps: Dissolving a first antimicrobial agent in a first solvent to obtain a first antimicrobial agent solution; wherein the first antimicrobial agent includes rifampicin, and the first solvent includes dichloromethane and / or tetrahydrofuran; Dissolving a second antibacterial agent in a second solvent to obtain a second antibacterial agent solution; wherein the second antibacterial agent includes clindamycin hydrochloride and / or minocycline, and the second solvent includes hexafluoroisopropanol; Mixing the first antimicrobial agent solution and the second antimicrobial agent solution uniformly to obtain the antimicrobial agent mixed solution; The catheter body is immersed in the antibacterial agent mixed solution, then taken out, and the first solvent and the second solvent are removed to obtain an antibacterial catheter.

10. The preparation method according to claim 9, It is characterized in that In the antimicrobial agent mixed solution, relative to the total volume of the first solvent and the second solvent, the mass-volume concentration of the first antimicrobial agent is 0.002 g / mL-2 g / mL, preferably 0.01 g / mL-1.0 g / mL, and the mass-volume concentration of the second antimicrobial agent is 0.002 g / mL-2 g / mL, preferably 0.01 g / mL-1.0 g / mL; and / or, The volume ratio of the first solvent to the second solvent is 1:(0.05-30), preferably 1:(0.1-10).

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