Antibacterial catheter and method of making same

Abstract

The application provides an antibacterial catheter and a preparation method thereof. The antibacterial catheter comprises a catheter body, a material of the catheter body comprises silica gel, and a solvent used in the preparation process of the antibacterial catheter comprises hexafluoroisopropanol. The catheter body is swelled by using the solvent, and an antibacterial agent is dispersed in the catheter body. Hexafluoroisopropanol of the application has a good swelling effect on the catheter body, so that the antibacterial agent can be well loaded on the catheter body. Moreover, the preparation process is simple, and when the antibacterial agent is dispersed in the catheter body, no additional alkalizing agent, penetrating agent or drug solubilizer (such as NaOH) needs to be added, and no subsequent treatment such as heating or high-pressure sterilization needs to be used.

Description

TECHNICAL FIELD

[0001] The present application relates to an antibacterial catheter and a preparation method thereof, and belongs to the technical field of drainage catheters. BACKGROUND

[0002] With the development of catheter diagnosis and treatment technology, the demand for medical catheters in clinical practice is increasing, with an annual usage of nearly 10 million cases. As a component of the shunt system, the external ventricular drainage catheter is used for cerebrospinal fluid drainage or shunt surgery in patients with hydrocephalus. During the intervention of the human brain, bacteria can easily adhere to the surface of the catheter and rapidly proliferate to form a bacterial biofilm, which can cause medical infection accidents and even lead to patient death in severe cases. Therefore, it is of great clinical application value and significance to prepare an external drainage catheter with anti-infection function.

[0003] Currently, the external drainage catheter with antibacterial function is mainly prepared by swelling loading method and surface coating method. For example, the invention patent application CN115154864A discloses an antibacterial and anti-adhesion super-smooth drainage catheter, which uses a surface coating method to coat polyvinylpyrrolidone on the outer surface of the catheter groove drainage section. The polyvinylpyrrolidone combines with water molecules to form a layer of hydrogel film coating, which can prevent the deposition of bacteria to a large extent, thereby playing an antibacterial role. However, the drainage catheter has the disadvantages of easy deposition of biological proteins on the surface of the coated catheter, which reduces the antibacterial effect, and the like when used for long-term implantation in the human body.

[0004] The commonly used solvents in the swelling loading method are dichloromethane, tetrahydrofuran, methanol and chloroform, and the commonly used antibacterial agents are rifampicin, clindamycin hydrochloride and minocycline, etc. However, the existing solvents have some shortcomings, such as poor light stability and high toxicity of chloroform, and poor swelling effect of methanol on the catheter body. Moreover, a single solvent cannot simultaneously dissolve multiple drugs, and it is even more difficult to achieve uniform loading of multiple drugs on the catheter.

[0005] In addition, the invention patent US10589003B2 discloses a method for coating or impregnating a non-organic surface with minocycline and rifampicin, using dichloromethane, tetrahydrofuran, chloroform, etc. as solvents to dissolve rifampicin and minocycline, to prepare an antibacterial catheter loaded with antibiotics. However, this method requires curing the coated or impregnated non-organic surface material at a temperature of at least about 40℃, and needs to heat dry the surface at a temperature of at least 50℃ for at least 12 hours, which has high energy consumption and a complicated preparation process.

[0006] Therefore, it is an urgent technical problem to develop an antibacterial catheter with high drug loading capacity, good antibacterial effect and simple preparation method. SUMMARY

[0007] Problems to be solved by the invention

[0008] In view of the technical problems existing in the prior art, the present application first provides an antibacterial catheter, the antibacterial catheter of the present application contains hexafluoroisopropanol in the solvent used in the preparation process, hexafluoroisopropanol has good swelling effect on silica gel catheter body, promotes the loading of antibacterial agent to the catheter body, and hexafluoroisopropanol is relatively friendly to the environment, reducing the use of other higher toxicity solvents.

[0009] The antibacterial catheter of the present application contains hexafluoroisopropanol in the solvent used in the preparation process, which can dissolve various antibacterial agents, especially suitable for dissolving clindamycin hydrochloride and minocycline, can be used as the solvent of the antibacterial agent and the swelling agent of the catheter body at the same time, makes the antibacterial agent solution have a higher concentration, and after swelling the catheter body, makes the catheter body have a higher drug loading, uniform drug loading, long-term drug release and good antibacterial effect.

[0010] Further, the present application also provides a preparation method of an antibacterial catheter, which is simple and easy to operate, raw materials are easy to obtain, and is suitable for mass production.

[0011] The preparation method of the present application dissolves drugs in groups, realizes the sufficient dissolution of various drugs, shortens the preparation time, and reduces the mutual influence between drug solutions.

[0012] Solution for solving the problem

[0013] The present application 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 swelled by using the solvent, and the antibacterial agent is dispersed inside the catheter body.

[0015] Further, the preparation process of the antibacterial catheter comprises dissolving the antibacterial agent by using the solvent to obtain an antibacterial agent solution, and swelling the catheter body by using the antibacterial agent solution, so that the antibacterial agent is dispersed inside the catheter body.

[0016] Further, the antibacterial agent comprises 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, the drug loading of the rifampicin is 0.040wt% or more, and the drug loading of the clindamycin hydrochloride or minocycline is 0.10wt% or more, based on the total mass of the antibacterial catheter being 100%.

[0019] Further, the antibacterial catheter has a drug release time of more than 14 days; the antibacterial catheter has an in-vitro antibacterial rate of more than 95% within 7 days; and / or,

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

[0021] Further, the tip of the antibacterial catheter has asymmetric drainage holes, and the maximum distance between two points on the profile line of the drainage holes is a major axis, and the minimum distance between two points on the profile line of the drainage holes is a minor axis;

[0022] Preferably, the antibacterial catheter has a first drainage hole and a second drainage hole, the major axis of the first drainage hole is greater than the major axis 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 major axis of the first drainage hole is 4.0mm-5.5mm, and the minor axis is 1.0mm-2.5mm; the major axis of the second drainage hole is 2.0mm-2.5mm, and the minor axis is 1.0mm-2.5mm.

[0024] The application also provides a preparation method of the antibacterial catheter, wherein the preparation method comprises swelling 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 comprising hexafluoroisopropanol to obtain the antibacterial agent solution.

[0025] Further, the antibacterial agent comprises clindamycin hydrochloride and / or minocycline, and the preparation method of the antibacterial catheter comprises 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] Further, the solvent used in the preparation process of the antibacterial catheter further comprises dichloromethane and / or tetrahydrofuran;

[0027] The antibacterial agent comprises rifampicin and clindamycin hydrochloride, or rifampicin and minocycline; and,

[0028] The preparation method comprises the following steps:

[0029] dissolving a first antibacterial agent in a first solvent to obtain a first antibacterial agent solution; wherein the first antibacterial agent comprises rifampicin, and the first solvent comprises dichloromethane and / or tetrahydrofuran;

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

[0031] mixing the first antibacterial agent solution and the second antibacterial agent solution uniformly to obtain the antibacterial agent mixed solution;

[0032] immersing the catheter body in the antibacterial agent mixed solution, and then taking out the catheter body to remove the first solvent and the second solvent, thereby obtaining the antibacterial catheter.

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

[0036] The catheter body of the antibacterial catheter of the application is swelled by a solvent, and the solvent used contains hexafluoroisopropanol, which has a good swelling effect on the catheter body containing silica gel. Therefore, the application does not need to add additional alkalizing agents, penetrating agents or drug solubilizers, etc. when dispersing the antibacterial agent in the catheter body, and does not need to use subsequent treatments such as heating or autoclaving.

[0037] Further, when the catheter body is swelled by mixing one or more than two other solvents with hexafluoroisopropanol, the swelling degree of the catheter body can be adjusted and enhanced.

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

[0039] Further, the antibacterial catheter of the application can load two or more 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 application has a high drug loading capacity for the loaded drugs, and has good antibacterial effect.

[0040] Further, the preparation method of the antibacterial catheter of the application is simple and easy to operate, the raw materials are easy to obtain, and it is suitable for mass production. Attached Figure Description

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

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

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

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

[0045] Figure 5 A schematic diagram of the structure of the antibacterial catheter of the present invention is shown; wherein, the left figure is the front view of the antibacterial catheter, and the right figure is the rear view of the antibacterial catheter. Detailed Implementation

[0046] Various exemplary embodiments, features, and aspects of the present invention will be described in detail below. The term "exemplary" as used herein means "serving as an example, embodiment, or illustration." Any embodiment described herein as "exemplary" is not necessarily to be construed as superior to or better than other embodiments.

[0047] Furthermore, to better illustrate the present invention, numerous specific details are set forth in the following detailed embodiments. Those skilled in the art should understand that the present invention can be practiced without certain specific details. In other instances, methods, means, apparatus, and steps well known to those skilled in the art have not been described in detail in order to highlight the spirit of the present invention.

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

[0049] In this specification, the word "may" has two meanings: to perform a certain process and not to perform a certain process.

[0050] In this specification, references to "some specific / preferred embodiments," "other specific / preferred embodiments," "implementation," etc., refer to specific elements (e.g., features, structures, properties, and / or characteristics) related to that embodiment, which are included in at least one of the embodiments described herein and may or may not be present in other embodiments. Furthermore, it should be understood that these elements may be combined in any suitable manner in various embodiments.

[0051] In this specification, the range of values ​​referred to as “value A - value B” is the range that includes the endpoint values ​​A and B.

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

[0053] In this instruction manual, the temperature referred to as "room temperature" or "normal temperature" can be 15-30℃, for example: 20-25℃.

[0054] <First Aspect>

[0055] A first aspect of the present invention provides an antibacterial catheter, the antibacterial catheter comprising a catheter body made of silicone, wherein the solvent used in the preparation process of the antibacterial catheter includes hexafluoroisopropanol, wherein...

[0056] The catheter body is swollen by using the solvent, thereby dispersing the antibacterial agent inside the catheter body.

[0057] The antibacterial catheter of the present invention includes a catheter body having an inlet (such as a drainage hole) and an outlet, the inlet and the outlet being connected through the catheter body to form a cavity structure. The material of the catheter body includes silicone.

[0058] Specifically, such as Figure 5 As shown, the tip of the antibacterial catheter has an asymmetrical drainage hole, and the maximum distance between two points passing through the center on the outline of the drainage hole is the major axis, and the minimum distance between two points passing through the center on the outline of the drainage hole is the minor axis.

[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 first drainage holes is less than the number of 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.

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

[0061] In this invention, the antibacterial catheter also has a ring of graduated lines that encircle the entire axis of the antibacterial catheter, facilitating observation of the insertion depth from different angles. Preferably, the distance between adjacent rings of graduated lines is 1 cm or 2 cm, and the midpoint distance between adjacent rings of graduated lines is marked with dot graduations. Furthermore, numbers are printed on at least both sides for easy reading.

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

[0063] Hexafluoroisopropanol can dissolve various antibacterial agents and has a good swelling effect on the catheter body. Therefore, the present application does not need to add additional alkalinizing agents, penetrating agents or drug solubilizers (such as NaOH) when dispersing antibacterial agents in the catheter body, nor does it need to use subsequent treatments such as heating or autoclaving.

[0064] In the present application, hexafluoroisopropanol can be used as a solvent for various antibacterial agents, which not only dissolves the antibacterial agents, but also penetrates and "swells" the entire catheter body, causing the internal channels of the catheter body to open, and the antibacterial agents to enter these channels, achieving uniform dispersion of the antibacterial agents in the catheter body. Therefore, hexafluoroisopropanol can also enable the drug-containing drainage catheter of the present application to achieve good loading and release effects of various antibacterial agents.

[0065] In the present application, the catheter body is swelled by using the solvent, and the antibacterial agents are penetrated into the inside of the catheter body. Specifically, the preparation process of the antibacterial catheter includes dissolving the antibacterial agents using the solvent to obtain an antibacterial agent solution; and using the antibacterial agent solution to swell the catheter body, so that the antibacterial agents are dispersed in the inside of the catheter body. Further, the antibacterial catheter of the present application can simultaneously load two or more antibacterial drugs, which can enhance the antibacterial synergy of the catheter, thereby improving the broad-spectrum antibacterial property of the catheter against various microorganisms. The antibacterial catheter of the present application also has a high drug loading capacity and 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, which can effectively resist various bacteria, including gram-positive and gram-negative bacteria. Clindamycin hydrochloride mainly plays a role by inhibiting the synthesis of bacterial proteins, and has good antibacterial effect on 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 the minocycline in the solvent to obtain the antibacterial agent solution, and then immersing the catheter body in the antibacterial agent solution, so that the antibacterial agents are dispersed in the inside of the catheter body.

[0068] In some specific embodiments, the solvent used in the preparation process of the antibacterial catheter further comprises dichloromethane and / or tetrahydrofuran. The inventors of the present application have found that the use of dichloromethane and / or tetrahydrofuran together with hexafluoroisopropanol for mixing with the catheter body can adjust and enhance the swelling degree of the catheter body, further increasing the drug loading amount.

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

[0070] In some specific embodiments, the drug loading amount of rifampicin is 0.040 wt% or more, for example, 0.040 wt%-0.1 wt%, based on the total mass of the antibacterial catheter; and the drug loading amount of clindamycin hydrochloride or minocycline is 0.10 wt% or more, for example, 0.10 wt%-0.2 wt%. The antibacterial catheter of the present application can simultaneously load two or more antibacterial drugs, which can enhance the antibacterial synergy of the catheter, thereby improving the broad-spectrum antibacterial property of the catheter against various microorganisms.

[0071] The antibacterial catheter of the present application 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 antibacterial catheter of the present application is suitable for preparing various medical implants, including but not limited to drainage catheters, vascular catheters, dialysis catheters, long-term tunnel 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-bound urinary devices, penile prostheses, vascular grafts, 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 application provides a preparation method of the antibacterial catheter according to the first aspect of the present application, which comprises immersing a 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 comprising hexafluoroisopropanol to obtain the antibacterial agent solution.

[0075] The present application can penetrate and "swell" the whole catheter body by using a solvent, so as to open the inner pores of the catheter body. Meanwhile, the antibacterial agent can enter the pores, so as to realize the uniform dispersion of the antibacterial agent in the catheter body.

[0076] The preparation method of the antibacterial catheter of the present application is simple. In the swelling and impregnation process of the catheter body, no additional alkalinizing agent, penetrating agent or drug solubilizer (such as NaOH) is needed, and no subsequent treatment such as heating or high-pressure sterilization is needed. After natural evaporation of the solvent and air-drying, a high drug loading and long-term antibacterial effect of various drugs on the catheter body can be realized.

[0077] In some specific embodiments, the antibacterial agent comprises clindamycin hydrochloride and / or minocycline, and the preparation method of the antibacterial catheter comprises dissolving the clindamycin hydrochloride and / or the minocycline in the solvent comprising hexafluoroisopropanol to obtain the antibacterial agent solution, and then impregnating the catheter body in the antibacterial agent solution to disperse the antibacterial agent in the catheter body.

[0078] In some specific embodiments, the solvent used in the preparation process of the antibacterial catheter further comprises dichloromethane and / or tetrahydrofuran; and the antibacterial agent comprises rifampicin and clindamycin hydrochloride, or rifampicin and minocycline. When the solvent and the antibacterial agent combination of the present embodiments are used, both the rifampicin and clindamycin hydrochloride, or the 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, improve the drug loading performance of the antibacterial catheter, and thus improve the antibacterial effect of the catheter, the preparation method comprises the following steps:

[0080] dissolving a first antibacterial agent in a first solvent to obtain a first antibacterial agent solution; wherein the first antibacterial agent comprises rifampicin, and the first solvent comprises 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 comprises clindamycin hydrochloride and / or minocycline, and the second solvent comprises hexafluoroisopropanol;

[0082] mixing the first antibacterial agent solution and the second antibacterial agent solution uniformly to obtain the antibacterial agent mixed solution;

[0083] immersing the catheter body in the antibacterial agent mixed solution, taking out the catheter body, and removing the first solvent and the second solvent to obtain the antibacterial catheter.

[0084] The present application can quickly realize complete dissolution of the first antibacterial agent and the second antibacterial agent, shorten the preparation time of the mixed solution of the first antibacterial agent and the second antibacterial agent, reduce the risk 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 mixed solution of the antibacterial agent, the mass-volume concentration of the first antibacterial agent can be 0.002 g / mL-2 g / mL, preferably 0.01 g / mL-1.0 g / mL, and the mass-volume concentration of the second antibacterial agent can be 0.002 g / mL-2 g / mL, preferably 0.01 g / mL-1.0 g / mL, relative to the total volume of the first solvent and the second solvent.

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

[0087] Further, in the present application, the catheter body is immersed in the mixed solution of the antibacterial agent, sealed and light-protected, and taken out after being immersed at room temperature for 0.5 h-1 h.

[0088] Further, the present application does not make special limitations on the method for removing the solvent, which can generally be volatilizing the solvent under natural conditions, for example, volatilizing the solvent in a fume hood at room temperature.

[0089] Further, the preparation method of the present application further comprises the step of post-treating the antibacterial catheter; preferably, the post-treatment comprises cleaning and then drying the antibacterial catheter. For drying, in order to not destroy the function of the antibacterial catheter, the present application can be air-dried at room temperature.

[0090] Examples

[0091] The embodiments of the present application will be described in detail below with reference to the examples, but those skilled in the art will understand that the following examples are only used to illustrate the present application and should not be regarded as limiting the scope of the present application. If no specific conditions are indicated in the examples, the conventional conditions or the conditions recommended by the manufacturer are used. If no manufacturer of the reagent or instrument is indicated, it is a conventional product that can be obtained by purchase.

[0092] Example 1

[0093] S1: Preparation of antibacterial agent solution

[0094] (1) Clindamycin hydrochloride 1.5 g was weighed and dissolved in 1.5 mL of hexafluoroisopropanol, stirred and dissolved to prepare a Clindamycin hydrochloride antiseptic solution with a mass-volume concentration of 1.0 g / mL.

[0095] S2: Preparation of an antibacterial catheter

[0096] A 1 cm long silica gel catheter was immersed in the above-mentioned antiseptic solution, sealed and protected from light, and after immersion at room temperature for 1 h, the silica gel catheter was removed and the excess solvent was volatilized under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then washed and finally left to dry at room temperature to obtain a clean antibacterial catheter product.

[0097] Example 2

[0098] S1: Preparation of an antiseptic solution

[0099] (1) Rifampicin 0.5 g was weighed and dissolved in 0.5 mL of hexafluoroisopropanol, stirred and dissolved to prepare a rifampicin antiseptic solution with a mass-volume concentration of 1.0 g / mL.

[0100] (2) Clindamycin hydrochloride 1.0 g was weighed and dissolved in 1.0 mL of hexafluoroisopropanol, stirred and dissolved to prepare a Clindamycin hydrochloride antiseptic solution with a mass-volume concentration of 1.0 g / mL.

[0101] (3) The rifampicin antiseptic solution and the Clindamycin hydrochloride antiseptic solution were mixed uniformly to prepare an antiseptic mixed solution; in the antiseptic mixed solution, the mass-volume concentration of rifampicin was 0.33 g / mL and the mass-volume concentration of Clindamycin hydrochloride was 0.67 g / mL, relative to the total volume of hexafluoroisopropanol.

[0102] S2: Preparation of an antibacterial catheter

[0103] A 1 cm long silica gel catheter was immersed in the above-mentioned antiseptic mixed solution, sealed and protected from light, and after immersion at room temperature for 1 h, the silica gel catheter was removed and the excess solvent was volatilized under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then washed and finally left to dry at room temperature to obtain a clean antibacterial catheter product.

[0104] Example 3

[0105] S1: Preparation of an antiseptic solution

[0106] (1) Rifampicin 0.008 g was weighed and dissolved in 0.5 mL of dichloromethane, stirred and dissolved to prepare a rifampicin antiseptic solution with a mass-volume concentration of 0.016 g / mL.

[0107] (2) Clindamycin hydrochloride 0.012 g was weighed and dissolved in 1.0 mL of hexafluoroisopropanol, stirred and dissolved to prepare a Clindamycin hydrochloride antiseptic solution with a mass-volume concentration of 0.012 g / mL.

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

[0109] S2: Preparation of an antibacterial catheter:

[0110] A 1 cm long silica gel catheter was immersed in the above-mentioned antiseptic mixed solution, sealed and protected from light, and after immersion at room temperature for 1 h, the silica gel catheter was taken out and the excess solvent was volatilized under a fume hood to obtain an antibacterial catheter. Then the antibacterial catheter was cleaned and finally placed at room temperature to air dry to obtain a clean antibacterial catheter product.

[0111] Example 4

[0112] S1: Preparation of an antiseptic solution:

[0113] (1) Rifampicin 0.008 g was weighed and dissolved in 0.5 mL of tetrahydrofuran, stirred and dissolved to prepare a rifampicin antiseptic solution with a mass-volume concentration of 0.016 g / mL.

[0114] (2) Clindamycin hydrochloride 0.012 g was weighed and dissolved in 1.0 mL of hexafluoroisopropanol, stirred and dissolved to prepare a Clindamycin hydrochloride antiseptic solution with a mass-volume concentration of 0.012 g / mL.

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

[0116] S2: Preparation of an antibacterial catheter:

[0117] A 1 cm long silica gel catheter was immersed in the above-mentioned antiseptic mixed solution, sealed and protected from light, and after immersion at room temperature for 1 h, the silica gel catheter was taken out and the excess solvent was volatilized under a fume hood to obtain an antibacterial catheter. Then the antibacterial catheter was cleaned and finally placed at room temperature to air dry to obtain a clean antibacterial catheter product.

[0118] Example 5

[0119] S1: Preparation of an antibacterial agent solution

[0120] (1) 0.008 g of rifampicin was weighed and dissolved in 0.8 mL of dichloromethane, and stirred to dissolve, to prepare a rifampicin antibacterial agent solution having a mass-volume concentration of 0.01 g / mL.

[0121] (2) 0.012 g of clindamycin hydrochloride was weighed and dissolved in 0.7 mL of hexafluoroisopropanol, and stirred to dissolve, to prepare a clindamycin hydrochloride antibacterial agent solution having a mass-volume concentration of 0.017 g / mL.

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

[0123] S2: Preparation of an antibacterial catheter

[0124] A 1 cm long silica gel catheter was immersed in the above antibacterial agent mixture solution, sealed and protected from light, and after immersion for 1 h at room temperature, the silica gel catheter was removed and excess solvent was volatilized under a fume hood to obtain an antibacterial catheter. The antibacterial catheter was then washed and finally left to dry at room temperature to obtain a clean antibacterial catheter product.

[0125] Example 6

[0126] S1: Preparation of an antibacterial agent solution

[0127] (1) 0.012 g of rifampicin was weighed and dissolved in 0.5 mL of tetrahydrofuran, and stirred to dissolve, to prepare a rifampicin antibacterial agent solution having a mass-volume concentration of 0.024 g / mL.

[0128] (2) 0.016 g of clindamycin hydrochloride was weighed and dissolved in 1.0 mL of hexafluoroisopropanol, and stirred to dissolve, to prepare a clindamycin hydrochloride antibacterial agent solution having a mass-volume concentration of 0.016 g / mL.

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

[0130] S2: Preparation of the antibacterial catheter

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

[0132] Example 7

[0133] S1: Preparation of the antibacterial agent solution

[0134] (1) 0.008 g of rifampicin was weighed and dissolved in 0.5 mL of dichloromethane, stirred and dissolved to prepare a rifampicin antibacterial agent solution with a mass-volume concentration of 0.016 g / mL.

[0135] (2) 0.012 g of minocycline was weighed and dissolved in 1.0 mL of hexafluoroisopropanol, stirred and dissolved to prepare a minocycline antibacterial agent solution with a mass-volume concentration of 0.012 g / mL.

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

[0137] S2: Preparation of the antibacterial catheter

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

[0139] Example 8

[0140] S1: Preparation of the antibacterial agent solution

[0141] (1) 0.008 g of rifampicin was weighed and dissolved in 0.5 mL of tetrahydrofuran, stirred and dissolved to prepare a rifampicin antibacterial agent solution with a mass-volume concentration of 0.016 g / mL.

[0142] (2) 0.012 g of minocycline was weighed and dissolved in 1.0 mL of hexafluoroisopropanol, stirred and dissolved to prepare a minocycline antibacterial agent solution with a mass-volume concentration of 0.012 g / mL.

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

[0144] S2: Preparation of the antibacterial catheter

[0145] A 1-cm-long silica gel catheter is immersed in the antibacterial agent mixed solution, sealed and protected from light, and after immersion at room temperature for 1 h, the silica gel catheter is taken out and the excess solvent is volatilized under a fume hood to obtain an antibacterial catheter. The antibacterial catheter is then cleaned, and finally left to air dry at room temperature to obtain a clean antibacterial catheter product.

[0146] Comparative Example 1

[0147] S1: Preparation of the antibacterial agent solution

[0148] Rifampicin 0.008 g and clindamycin hydrochloride 0.012 g are weighed into 1.5 mL of dichloromethane, stirred and dissolved to obtain an antibacterial agent mixed solution; wherein in the antibacterial agent mixed solution, the mass-volume concentration of rifampicin is 0.0053 g / mL relative to the volume of dichloromethane, and clindamycin hydrochloride forms a precipitate.

[0149] S2: Preparation of the antibacterial catheter

[0150] A 1-cm-long silica gel catheter is immersed in the antibacterial agent mixed solution from which the precipitate is removed, sealed and protected from light, and after immersion at room temperature for 1 h, the silica gel catheter is taken out and the excess solvent is volatilized under a fume hood to obtain an antibacterial catheter. The antibacterial catheter is then cleaned, and finally left to air dry at room temperature to obtain a clean antibacterial catheter.

[0151] Comparative Example 2

[0152] S1: Preparation of the antibacterial agent solution

[0153] Rifampicin 0.008 g and clindamycin hydrochloride 0.012 g are weighed into 1.5 mL of tetrahydrofuran, stirred and dissolved to obtain an antibacterial agent mixed solution; wherein in the antibacterial agent mixed solution, the mass-volume concentration of rifampicin is 0.0053 g / mL relative to the volume of solvent, and clindamycin hydrochloride forms a precipitate.

[0154] S2: Preparation of the antibacterial catheter

[0155] The 1 cm long silicone catheter was immersed in the anti-microbial mixed solution from which the precipitate was removed, sealed and kept away from light, and then taken out after being immersed at room temperature for 1 h. The excess solvent was volatilized under a fume hood to obtain the anti-microbial catheter. The anti-microbial catheter was then cleaned and finally left to dry at room temperature to obtain the clean anti-microbial catheter.

[0156] Comparative Example 3

[0157] S1: Preparation of an anti-microbial solution

[0158] Rifampicin 0.008 g and clindamycin hydrochloride 0.012 g were weighed into 1.5 mL of methanol, stirred and dissolved to prepare an anti-microbial mixed solution. In the anti-microbial mixed solution, the mass-volume concentration of rifampicin was 0.0053 g / mL and the mass-volume concentration of clindamycin hydrochloride was 0.008 g / mL relative to the volume of the solvent.

[0159] S2: Preparation of an anti-microbial catheter

[0160] The 1 cm long silicone catheter was immersed in the anti-microbial mixed solution from which the precipitate was removed, sealed and kept away from light, and then taken out after being immersed at room temperature for 1 h. The excess solvent was volatilized under a fume hood to obtain the anti-microbial catheter. The anti-microbial catheter was then cleaned and finally left to dry at room temperature to obtain the clean anti-microbial catheter.

[0161] Comparative Example 4

[0162] S1: Preparation of an anti-microbial solution

[0163] (1) Rifampicin 0.008 g was weighed and dissolved in 0.5 mL of acetonitrile to prepare a rifampicin anti-microbial solution with a mass-volume concentration of 0.016 g / mL.

[0164] (2) Clindamycin hydrochloride 0.012 g was weighed and added to 1.0 mL of methanol, stirred and dissolved to prepare a clindamycin hydrochloride anti-microbial solution with a mass-volume concentration of 0.008 g / mL.

[0165] (3) The rifampicin anti-microbial solution was mixed uniformly with the precipitate-removed clindamycin hydrochloride anti-microbial solution to prepare an anti-microbial mixed solution. In the anti-microbial mixed solution, the mass-volume concentration of rifampicin was 0.0053 g / mL and the mass-volume concentration of clindamycin hydrochloride was 0.008 g / mL relative to the total volume of methanol and acetonitrile.

[0166] S2: Preparation of an anti-microbial catheter

[0167] The 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 h, the silicone catheter was taken out and the excess solvent was volatilized under a fume hood to obtain an antibacterial catheter. Then the antibacterial catheter was cleaned and finally placed at room temperature to dry to obtain a clean antibacterial catheter product.

[0168] Performance test

[0169] 1. Swelling property test

[0170] The volume swelling degree was used to evaluate the swelling property of the antibacterial catheter of Examples 1-8 and Comparative Examples 1-4 during preparation. The silicone catheter of a certain length was cut and immersed in the corresponding solvent of Examples 1-8 and Comparative Examples 1-4 for a certain time, and after swelling equilibrium, 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 of antibacterial catheter during preparation

[0172] Example / Comparative example Volume swell (%) 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] As can be seen from Table 1, compared with Comparative Example 3 and Comparative Example 4, the volume swelling degree of the antibacterial catheter of the present application after swelling equilibrium is higher, and hexafluoroisopropanol has a good swelling effect on the catheter body, which is beneficial to loading more antibacterial agent solution in the antibacterial catheter.

[0174] 2. Drug loading

[0175] The antibacterial catheter of Examples 1-8 and Comparative Examples 1-4 of a certain length was cut and immersed in chloroform for a certain time, the drug particles were obtained by thoroughly volatilizing the chloroform, the drug was dissolved, the drug concentration was determined using a liquid chromatograph, and the content of each drug in the antibacterial catheter (i.e. drug loading) was calculated. The calculation formula of drug loading is: drug loading = (mass of single drug / mass of drug-loaded silicone catheter) * 100%. The results are shown in Table 2 and Table 3 below. Table 2 is the drug loading of the antibacterial catheter of Examples 1-8, and Table 3 is the drug loading of the antibacterial catheter 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 N.D. 2 0.0386±0.00005 N.D. 3 0.0008±0.000002 0.0003±0.000002 4 N.D. N.D.

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

[0181] However, in Comparative Examples 1-2, although the swelling degree of the antibacterial catheter of Comparative Example 1 and Comparative Example 2 is high, since clindamycin hydrochloride is not dissolved, the drug loading amount of clindamycin hydrochloride cannot be detected. In Comparative Example 3, the swelling degree of the catheter by methanol is low, and even if a certain amount of clindamycin hydrochloride can be dissolved, the drug loading amount of rifampicin and clindamycin hydrochloride is extremely small. In Comparative Example 4, the conventional complex solvent hardly swells the antibacterial catheter, and hardly allows the antibacterial agent mixed solution to penetrate into the inside of the catheter, so the drug loading amount of rifampicin and clindamycin hydrochloride cannot be detected. It can be seen that the solvent including hexafluoroisopropanol in the present application can better swell the catheter, and has good solubility to the antibacterial agent, so that the antibacterial catheter has better drug loading effect.

[0182] In addition, from the apparent color depth of Figure 1 and Figure 2 it can be seen 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. Antibacterial activity

[0184] 3. Antibacterial activity The antibacterial catheter prepared in Example 3 was cut to a certain length, and was placed in a staphylococcus aureus suspension of a certain concentration, and was then incubated at 37°C, and the staphylococcus aureus suspension was used as a blank control group. Every 1 day, the drainage tube was taken out and was immersed in a new staphylococcus aureus suspension test tube, and at the same time, the blank control group was replaced with a new bacteria suspension tube. Three samples at 1 day and 7 days of incubation were taken, and the bacteria suspension at the end of incubation was taken, was diluted, and was subjected to bacterial colony counting by the spread plate method. Compared with the blank control group, the antibacterial rate was calculated. The calculation formula of the antibacterial rate was: antibacterial rate=(bacterial colony count of the blank control group-bacterial colony count of the sample group) / bacterial colony count of the blank control group x 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 uses a solvent-swellable silicone catheter containing hexafluoroisopropanol to load at least two antibacterial drugs, which can achieve a high drug loading of multiple antibacterial agents in a short time. Moreover, the prepared antibacterial catheter has low-concentration sustained release and long-lasting antibacterial effect, thereby enhancing the antibacterial synergy of the catheter and improving the broad-spectrum antibacterial activity of the catheter against multiple microorganisms.

[0188] 4. Sustained release time

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

[0190] The release curves of rifampin and clindamycin hydrochloride in the antibacterial catheter prepared in Example 3 are as follows: Figure 3 and Figure 4 As shown, rifampin and clindamycin hydrochloride in the antibacterial catheter can be slowly released at low concentrations over a period of up to 350 hours, preventing bacterial colonization on the surface of the antibacterial catheter. Furthermore, the in vitro antibacterial rate results in Table 4 show that even with daily replacement of the bacterial solution, the antibacterial rate of the catheter remains greater than 95% after 7 days.

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

[0192] The various embodiments of the present invention have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles, practical application, or technical improvements to the embodiments in the market, or to enable others skilled in the art to understand the embodiments disclosed herein.

Claims

1. An antibacterial catheter, characterized in that, The antibacterial catheter comprises a catheter body, the material of the catheter body is silica gel, the solvent used in the preparation process of the antibacterial catheter comprises hexafluoroisopropanol and dichloromethane, or comprises hexafluoroisopropanol and tetrahydrofuran, wherein, The catheter body is swelled by using the solvent, and the antibacterial agent is dispersed inside the catheter body; The antibacterial agent comprises rifampicin and clindamycin hydrochloride, or rifampicin and minocycline.

2. The antimicrobial catheter of claim 1, wherein, The preparation process of the antibacterial catheter comprises dissolving the antibacterial agent in the solvent to obtain an antibacterial agent solution, and swelling the catheter body by using the antibacterial agent solution, so that the antibacterial agent is dispersed inside the catheter body.

3. The antibacterial catheter according to claim 1 or 2, characterized in that, The drug loading amount of the rifampicin is greater than or equal to 0.040 wt%, and the drug loading amount of the clindamycin hydrochloride or minocycline is greater than or equal to 0.10 wt%, based on the total mass of the antibacterial catheter.

4. The antimicrobial catheter of claim 1 or 2, wherein, The drug 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.

5. The antimicrobial catheter of claim 4, wherein, The antibacterial catheter is a drainage catheter for cerebrospinal fluid drainage.

6. The antimicrobial catheter of claim 1 or 2, wherein, The tip of the antibacterial catheter has asymmetric drainage holes, and the maximum distance between two points on the profile line of the drainage holes passing through the center is a major diameter, and the minimum distance between two points on the profile line of the drainage holes passing through the center is a minor diameter.

7. The antimicrobial catheter of claim 6, wherein, The antibacterial catheter has first drainage holes and second drainage holes, the major diameter of the first drainage holes is greater than the major diameter of the second drainage holes, and / or the number of the first drainage holes is less than the number of the second drainage holes.

8. The antimicrobial catheter of claim 7, wherein, The major diameter of the first drainage holes is 4.0 mm-5.5 mm, and the minor diameter is 1.0 mm-2.5 mm; the major diameter of the second drainage holes is 2.0 mm-2.5 mm, and the minor diameter is 1.0 mm-2.5 mm.

9. A preparation method of the antibacterial catheter according to any one of claims 1-8, wherein, The preparation method comprises swelling the catheter body in an antibacterial agent solution, so that the antibacterial agent is dispersed inside the catheter body; wherein the antibacterial agent is dissolved in a solvent comprising hexafluoroisopropanol to obtain the antibacterial agent solution.

10. The method of claim 9, wherein, The antibacterial agent comprises clindamycin hydrochloride and / or minocycline, and the preparation method of the antibacterial catheter comprises 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, so that the antibacterial agent is dispersed inside the catheter body.

11. The method of claim 10, wherein, The solvent used in the preparation process of the antibacterial catheter further comprises dichloromethane and / or tetrahydrofuran; The antibacterial agent comprises rifampicin and clindamycin hydrochloride, or rifampicin and minocycline; and, The preparation method comprises the following steps: dissolving a first antibacterial agent in a first solvent to obtain a first antibacterial agent solution; wherein the first antibacterial agent comprises rifampicin, and the first solvent comprises 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 comprises clindamycin hydrochloride and / or minocycline, and the second solvent comprises hexafluoroisopropanol. mixing the first antibacterial agent solution and the second antibacterial agent solution to obtain the antibacterial agent mixed solution; immersing the catheter body in the antibacterial agent mixed solution, and then taking out the catheter body to remove the first solvent and the second solvent, thereby obtaining the antibacterial catheter.

12. The method of claim 11, wherein, In the antibacterial agent mixed solution, the mass-volume concentration of the first antibacterial agent is 0.002 g / mL-2 g / mL, and the mass-volume concentration of the second antibacterial agent is 0.002 g / mL-2 g / mL, relative to the total volume of the first solvent and the second solvent; and / or, The volume ratio of the first solvent to the second solvent is 1:(0.05-30).

13. The method of claim 12, wherein, In the antibacterial agent mixed solution, the mass-volume concentration of the first antibacterial agent is 0.01 g / mL-1.0 g / mL, and the mass-volume concentration of the second antibacterial agent is 0.01 g / mL-1.0 g / mL, relative to the total volume of the first solvent and the second solvent; and / or, The volume ratio of the first solvent to the second solvent is 1:(0.1-10).

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