Highly efficient antibacterial tracheal cannula and preparation method thereof

Abstract

This invention provides a highly effective antibacterial endotracheal tube and its preparation method, relating to the field of medical implant materials technology. The method includes the following steps: S1: Ofloxacin is placed in a first activating agent for a first activation treatment to obtain activated ofloxacin, which contains amide groups; S2: Salbutamol is placed in a second activating agent for a second activation treatment to obtain activated salbutamol, which contains ether groups; S3: A silicone endotracheal tube is subjected to a third activation treatment to obtain an activated silicone endotracheal tube, the surface of which contains silanol groups; S4: Activated ofloxacin and activated salbutamol are grafted onto the surface of the activated silicone endotracheal tube to obtain a highly effective antibacterial endotracheal tube. This invention, by activating ofloxacin and salbutamol separately and attaching them to the surface of the silicone endotracheal tube, endows the endotracheal tube with highly effective antibacterial properties and tracheal adaptability.

Description

Technical Field

[0001] This invention relates to the field of medical implant materials technology, and in particular to a highly efficient antibacterial endotracheal tube and its preparation method. Background Technology

[0002] Silicone, as a high-performance medical material, is widely used in the medical field due to its unique physicochemical properties and biocompatibility, especially in the manufacture of endotracheal tubes, where it demonstrates significant advantages. Silicone endotracheal tubes not only possess good elasticity and flexibility, conforming to the airway structure and reducing discomfort and damage during intubation, but also, due to their chemical stability, are less likely to cause allergic or rejection reactions, thus ensuring patient safety and comfort. However, despite significant advancements in the design and material selection of silicone endotracheal tubes, some challenges remain in clinical application. The most prominent issues are insufficient antibacterial properties and the potential for respiratory complications after intubation.

[0003] Endotracheal intubation, as a necessary emergency and surgical aid, artificially establishes an airway to ensure unobstructed breathing for patients. However, this invasive procedure inevitably breaks down the airway's natural defenses, allowing external bacteria, viruses, and other microorganisms to enter and increasing the risk of infection. Especially when the endotracheal tube is left in place for an extended period, the airway microenvironment changes, making it easier for bacteria to colonize and multiply on the tube surface and inside the airway, leading to respiratory infections. While silicone endotracheal tubes have a smooth surface that helps reduce bacterial adhesion, they do not possess the ability to actively kill or inhibit bacteria, which limits their effectiveness in preventing infection.

[0004] More seriously, endotracheal intubation can interfere with the patient's cough reflex, a crucial mechanism for clearing respiratory secretions and foreign objects. Normally, coughing effectively expels phlegm, food debris, and other substances, keeping the airways clean and clear. However, after intubation, the cough reflex is suppressed, preventing the effective expulsion of phlegm and other excrement, which tend to accumulate in the trachea and inside the tube. Over time, these excrement dry and solidify, forming phlegm crusts, mucus plugs, and other blockages. These not only obstruct airway patency but can also become a breeding ground for bacteria, further increasing the risk of respiratory infections.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The purpose of this invention is to provide a highly efficient antibacterial endotracheal tube and its preparation method. By activating ofloxacin and salbutamol respectively, they are attached to the surface of the silicone endotracheal tube, giving the endotracheal tube highly efficient antibacterial properties and endotracheal adaptability.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] This invention provides a method for preparing a highly effective antibacterial endotracheal tube, comprising the following steps:

[0009] S1: Ofloxacin is placed in a first activator for a first activation treatment to obtain activated ofloxacin, which contains an amide group;

[0010] S2: Salbutamol is placed in a second activator for a second activation treatment to obtain activated salbutamol, which contains an ether group;

[0011] S3: Perform a third activation treatment on the silicone endotracheal tube to obtain an activated silicone endotracheal tube. The surface of the activated silicone endotracheal tube contains silanol groups.

[0012] S4: Activated ofloxacin and activated salbutamol are grafted onto the surface of activated silicone endotracheal tubes to obtain highly effective antibacterial endotracheal tubes.

[0013] Furthermore, based on the above technical solution, the first activator includes one or more of the following: diphenylmethane diisocyanate, isophorone diisocyanate, hexamethylene diisocyanate, and naphthalene diisocyanate;

[0014] And / or, the second activator includes one or more of ethylene oxide, propylene oxide, epichlorohydrin, phenylene oxide, and 1,2-epoxybutane.

[0015] Furthermore, based on the above technical solution, in step S1, the first activation process includes:

[0016] S11: Place ofloxacin in a solvent and stir to obtain ofloxacin solution;

[0017] S12: Place the first activator in a solvent and stir to obtain a first activator solution;

[0018] S13: Add the first activator solution dropwise to the ofloxacin solution, stir, then add water to the reaction solution, filter, take the solid mixture, wash, purify, and dry to obtain activated ofloxacin.

[0019] Furthermore, based on the above technical solution, the solvents in steps S11 and S12 each include one or more of dichloromethane, acetone, and dimethyl sulfoxide.

[0020] And / or, the molar ratio of ofloxacin in the ofloxacin solution to the first activator in the first activator solution is 1:(1-3);

[0021] And / or, in step S13, the reaction conditions include: a reaction temperature of 30-50℃, a dropping rate of (1-2) mL / min, and a reaction time of 10-24 h after the dropping is completed;

[0022] And / or, add water to the reaction solution to precipitate the reactants, filter and take the solid mixture, wash with water 1-3 times, purify by recrystallization, and dry at 50-80℃ for 24-48h.

[0023] Furthermore, based on the above technical solution, in step S2, the second activation treatment includes:

[0024] S21: Place salbutamol in a solvent and stir to obtain a salbutamol solution;

[0025] S22: Place the second activator in a solvent and stir to obtain a solution of the second activator;

[0026] S23: Add the second activator solution dropwise to the salbutamol solution, stir, then add water to the reaction solution, filter, take the solid mixture, wash, purify, and dry to obtain activated salbutamol.

[0027] Furthermore, based on the above technical solution, the solvents in steps S21 and S22 each include one or more of dichloromethane, tetrahydrofuran, and ethyl acetate;

[0028] And / or, the molar ratio of salbutamol in the salbutamol solution to the second activator in the second activator solution is 1:(1-3), such as 1:1.5, 1:2, 1:2.5, etc.;

[0029] And / or, in step S23, the reaction conditions include: pH 8-9, reaction temperature 30-50℃, dropping rate (1-2) mL / min, and reaction time 10-24 h after dropping is completed;

[0030] And / or, water is added to the reaction solution to precipitate the reactants. After filtration, the solid mixture is washed with water 1-3 times. Purification is carried out by recrystallization and drying at 50-80℃ for 24-48 hours.

[0031] Furthermore, based on the above technical solution, in step S3, the third activation treatment is oxygen plasma treatment, and the oxygen plasma treatment conditions are: power 70-90W, gas flow rate 90-110mL / min, gas pressure 50-70Pa, and etching time 30-60s.

[0032] Furthermore, based on the above technical solution, step S4 specifically includes the following steps:

[0033] S41: Place the activated ofloxacin obtained in step S1 into a solvent and stir to obtain an activated ofloxacin solution.

[0034] S42: Place the activated salbutamol obtained in step S2 into a solvent and stir to obtain an activated salbutamol solution;

[0035] S43: Mix the activated ofloxacin solution and the activated salbutamol solution, stir to obtain a mixed solution, and then immerse the activated silicone endotracheal tube in the mixed solution to obtain a highly effective antibacterial endotracheal tube.

[0036] Furthermore, based on the above technical solution, the solvents in steps S41 and S42 each include one or more of dimethyl sulfoxide, dichloromethane, and acetone.

[0037] And / or, step S43 includes: mixing activated ofloxacin solution and activated salbutamol solution at 40-60℃ and stirring for 4-6 hours to obtain a mixed solution; immersing the activated silicone endotracheal tube in the mixed solution for 5-10 minutes; slowly removing it and placing it in a sealed container with a humidity of 80-100%; drying it at 50-70℃ for 25-35 minutes; repeating this process 2-4 times; then removing the silicone endotracheal tube and placing it in a sealed container with a humidity of 80-100%; and placing it at 45-55℃ for 15-24 hours to obtain a highly effective antibacterial endotracheal tube.

[0038] The present invention also provides a highly efficient antibacterial endotracheal tube prepared by the preparation method described above.

[0039] The present invention provides a highly efficient antibacterial endotracheal tube and its preparation method, with the following beneficial effects:

[0040] This invention involves the activation treatment of ofloxacin and salbutamol. An amide group is grafted onto the molecular structure of ofloxacin through a specific chemical reaction. This group not only enhances the activity of ofloxacin but also provides a possibility for its subsequent immobilization. Simultaneously, salbutamol is also activated, with an ether group grafted onto its molecule. This group also provides conditions for its binding to the silica gel surface. After preparation, the surface of the silica gel endotracheal tube is also activated, enriching its surface with silanol groups, providing reaction sites for the immobilization of ofloxacin and salbutamol. In the design of this invention, the amide group on ofloxacin and the ether group on salbutamol both possess good stability, preventing unnecessary chemical reactions between them and maintaining their respective chemical activities. Furthermore, ofloxacin and salbutamol are two different drugs with significant differences in their molecular structures, therefore they will not react with each other under normal conditions. This feature is particularly important in the application of this invention because it ensures that no cross-linking reaction occurs when ofloxacin and salbutamol react with the silanol groups on the silicone endotracheal tube, thus avoiding unnecessary structural changes and functional losses. Therefore, when ofloxacin and salbutamol are respectively fixed on the surface of the silicone endotracheal tube, their amide and ether groups can be safely allowed to react with the silanol groups to form stable chemical bonds. This not only achieves effective drug fixation but also maintains drug activity, providing the endotracheal tube with highly efficient antibacterial and tracheal adaptability functions, while also ensuring the safety and reliability of the endotracheal tube. Detailed Implementation

[0041] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Those skilled in the art should understand that the embodiments described are merely illustrative of the invention and should not be considered as specific limitations thereof. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention. Process parameters not specifically specified in the following embodiments are generally performed under conventional conditions.

[0042] The endpoints and any values ​​of the ranges disclosed in this invention are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this invention.

[0043] According to a first aspect of the present invention, a method for preparing a highly effective antibacterial endotracheal tube is provided, comprising the following steps:

[0044] S1: Ofloxacin is placed in a first activator for a first activation treatment to obtain activated ofloxacin, which contains an amide group;

[0045] S2: Salbutamol is placed in a second activator for a second activation treatment to obtain activated salbutamol, which contains an ether group;

[0046] S3: Perform a third activation treatment on the silicone endotracheal tube to obtain an activated silicone endotracheal tube. The surface of the activated silicone endotracheal tube contains silanol groups.

[0047] S4: Activated ofloxacin and activated salbutamol are grafted onto the surface of activated silicone endotracheal tubes to obtain highly effective antibacterial endotracheal tubes.

[0048] Specifically, this invention activates ofloxacin and salbutamol separately: An amide group is grafted onto the molecular structure of ofloxacin through a specific chemical reaction. This group not only enhances the activity of ofloxacin but also provides a possibility for its subsequent immobilization. Simultaneously, salbutamol is also activated, with an ether group grafted onto its molecule. This group also provides conditions for its binding to the silica gel surface. After preparation, the surface of the silica gel endotracheal tube is also activated, enriching its surface with silanol groups, providing reaction sites for the immobilization of ofloxacin and salbutamol. In the design of this invention, the amide group on ofloxacin and the ether group on salbutamol both possess good stability, preventing unnecessary chemical reactions between them and maintaining their respective chemical activities. Furthermore, ofloxacin and salbutamol are two different drugs with significant differences in their molecular structures, therefore they will not react with each other under normal conditions. This feature is particularly important in the application of this invention because it ensures that no cross-linking reaction occurs when ofloxacin and salbutamol react with the silanol groups on the silicone endotracheal tube, thus avoiding unnecessary structural changes and functional losses. Therefore, when ofloxacin and salbutamol are respectively fixed on the surface of the silicone endotracheal tube, their amide and ether groups can be safely allowed to react with the silanol groups to form stable chemical bonds. This not only achieves effective drug fixation but also maintains drug activity, providing the endotracheal tube with highly efficient antibacterial and tracheal adaptability functions, while also ensuring the safety and reliability of the endotracheal tube.

[0049] As an optional embodiment of the present invention, the first activator includes one or more of diphenylmethane diisocyanate, isophorone diisocyanate, hexamethylene diisocyanate, and naphthalene diisocyanate.

[0050] Specifically, the fluorine atom and quinolone ring structure in the ofloxacin molecule are key. They effectively block the normal replication and transcription of bacterial DNA by tightly binding to the A subunit of bacterial DNA gyrase. This binding not only prevents the unwinding and rewinding of bacterial DNA but also leads to DNA strand breaks, thereby inhibiting bacterial growth and reproduction. To protect the unique antibacterial functional groups in ofloxacin, this invention uses isocyanate activators to activate ofloxacin. During the activation process of ofloxacin, the reaction of isocyanate compounds mainly focuses on coupling with other specific functional groups in the ofloxacin molecule, without directly affecting the fluorine atom and quinolone ring structure. This is because the reactivity of isocyanate compounds is mainly concentrated on their isocyanate groups, which tend to react with the carboxyl functional groups in the ofloxacin molecule to form stable chemical bonds. The fluorine atom and quinolone ring structure in ofloxacin are not affected by isocyanate compounds.

[0051] Secondly, isocyanate activators operate under relatively mild reaction conditions during the activation of drug molecules, avoiding the potential damage to the molecular structure of ofloxacin caused by extreme conditions such as high temperature, strong acid, and strong alkali, thus ensuring that the pharmacological properties of ofloxacin are not affected after activation.

[0052] In addition, isocyanate activators have good biocompatibility and low toxicity. The byproducts released during the activation process are usually harmless to the human body, and the activated ofloxacin molecules can maintain stable chemical properties in the body without causing unnecessary biological reactions or toxic effects.

[0053] And / or, the second activator includes one or more of ethylene oxide, propylene oxide, epichlorohydrin, phenylene oxide, and 1,2-epoxybutane.

[0054] Specifically, salbutamol is a commonly used β2 receptor agonist with functional groups such as alcohol and amine groups on its surface. The amine group on the surface of salbutamol is key to its efficacy; it can bind to β2 adrenergic receptors, activate these receptors, leading to relaxation of bronchial smooth muscle, relieving bronchospasm, and thus alleviating symptoms such as difficulty breathing during an asthma attack.

[0055] This invention activates salbutamol using an epoxy group compound because, in the salbutamol molecule, the epoxy group compound preferentially reacts with the hydroxyl group of salbutamol rather than with its amino group. This selectivity stems from the kinetic advantage of the reaction between the hydroxyl group and the epoxy group, as well as the strong nucleophilicity of the amino group itself. This property makes it difficult for the amino group to react directly with the epoxy group compound under normal conditions. After the epoxy group compound reacts with the hydroxyl group of salbutamol, it generates the corresponding ether compound. This chemical reaction not only stabilizes the structure of salbutamol but also avoids interference with the amino group, which is crucial to its pharmacological efficacy. The amino group is a key functional group for salbutamol to exert its β2-adrenergic receptor agonist effect, and its integrity is essential for maintaining the drug's biological activity. Therefore, by selectively reacting with the hydroxyl group, this invention ensures that the core pharmacologically active structure of salbutamol is completely preserved during the activation process. Furthermore, the ether bond generated by the reaction of the epoxy group compound with the hydroxyl group on the surface of salbutamol provides a reliable fixation site for salbutamol.

[0056] As an optional embodiment of the present invention, in step S1, the first activation process includes:

[0057] S11: Place ofloxacin in a solvent and stir to obtain ofloxacin solution;

[0058] S12: Place the first activator in a solvent and stir to obtain a first activator solution;

[0059] S13: Add the first activator solution dropwise to the ofloxacin solution, stir, then add water to the reaction solution, filter, take the solid mixture, wash, purify, and dry to obtain activated ofloxacin.

[0060] As an optional embodiment of the present invention, the solvents in steps S11 and S12 include one or more of dichloromethane, acetone, and dimethyl sulfoxide.

[0061] And / or, the molar ratio of ofloxacin in the ofloxacin solution to the first activator in the first activator solution is 1:(1-3), such as 1:1.5, 1:2, 1:2.5, etc.;

[0062] Specifically, this invention limits the molar ratio of ofloxacin in the ofloxacin solution to isocyanate in the isocyanate activator solution to 1:(1-3). This ensures that the amide groups on the ofloxacin molecule can undergo a grafting reaction with the isocyanate to a suitable degree. This not only preserves the original pharmacological activity of ofloxacin but also significantly enhances the binding ability of ofloxacin to the silicone endotracheal tube. This enhanced binding force is crucial for achieving controlled drug release, targeted drug delivery, and improving drug stability and bioavailability in vivo. Furthermore, it reduces unnecessary side reactions, such as excessive cross-linking and hydrolysis, which could reduce the purity of the target product or even produce toxic or harmful substances.

[0063] And / or, in step S13, the reaction conditions include: a reaction temperature of 30-50℃, a dropping rate of (1-2) mL / min, and a reaction time of 10-24 h after the dropping is completed;

[0064] And / or, add water to the reaction solution to precipitate the reactants, filter and take the solid mixture, wash with water 1-3 times, purify by recrystallization, and dry at 50-80℃ for 24-48h.

[0065] As an optional embodiment of the present invention, step S2 includes the following:

[0066] S21: Place salbutamol in a solvent and stir to obtain a salbutamol solution;

[0067] S22: Place the second activator in a solvent and stir to obtain a solution of the second activator;

[0068] S23: Add the second activator solution dropwise to the salbutamol solution, stir, then add water to the reaction solution, filter, take the solid mixture, wash, purify, and dry to obtain activated salbutamol.

[0069] As an optional embodiment of the present invention, the solvents in steps S21 and S22 include one or more of dichloromethane, tetrahydrofuran, ethyl acetate, acetone, and dimethyl sulfoxide.

[0070] And / or, the molar ratio of salbutamol in the salbutamol solution to the second activator in the second activator solution is 1:(1-3), such as 1:1.5, 1:2, 1:2.5, etc.;

[0071] Specifically, this invention limits the molar ratio of salbutamol in the salbutamol solution to that of the epoxy compound in the epoxy compound activator solution to 1:(1-3). The purpose is to precisely control the reaction process and ensure that the hydroxyl groups in the salbutamol molecule undergo an efficient and controllable grafting reaction with the epoxy compound. This enhances the binding force of salbutamol to the silicone endotracheal tube while retaining its original pharmacological activity, and reduces unnecessary side reactions, thereby improving the purity and stability of the target product.

[0072] And / or, in step S23, the reaction conditions include: pH 8-9, reaction temperature 30-50℃, dropping rate (1-2) mL / min, and reaction time 10-24 h after dropping is completed;

[0073] And / or, water is added to the reaction solution to precipitate the reactants. After filtration, the solid mixture is washed with water 1-3 times. Purification is carried out by recrystallization and drying at 50-80℃ for 24-48 hours.

[0074] As an optional embodiment of the present invention, in step S3...

[0075] The third activation treatment is oxygen plasma treatment, and the oxygen plasma treatment conditions are: power 70-90W, gas flow rate 90-110mL / min, gas pressure 50-70Pa, and etching time 30-60s.

[0076] Specifically, this invention activates silicone endotracheal tubes using oxygen plasma, increasing the surface of the tubes with a large number of active silanol groups. The introduction of these active silanol groups provides abundant reaction sites for subsequent grafting reactions. This allows the silicone endotracheal tube surface to more easily chemically bond with the amide groups on ofloxacin and the ether groups on salbutamol. The carbonyl oxygen atom in the amide group can form hydrogen bonds with the hydrogen atoms in the silanol group, further forming covalent bonds through condensation reactions, thus firmly fixing ofloxacin to the silicone endotracheal tube surface. Similarly, the oxygen atom in the ether group on salbutamol can form hydrogen bonds with the hydrogen atoms in the silanol group, subsequently forming silicon-oxygen bonds through condensation reactions between the silanol groups, thus fixing salbutamol to the silicone endotracheal tube surface. This achieves improved immobilization, targeted drug delivery, and biocompatibility of ofloxacin and salbutamol, and further enhances the high antibacterial efficiency and tracheal adaptability of the endotracheal tube. Furthermore, the presence of active silanol groups also enhances the hydrophilicity of the silicone endotracheal tube surface. Improved hydrophilicity helps reduce the adhesion and growth of bacteria and other microorganisms on silicone surfaces, thereby reducing the risk of infection.

[0077] As an optional embodiment of the present invention, step S4 specifically includes the following steps:

[0078] S41: Place the activated ofloxacin obtained in step S1 into a solvent and stir to obtain an activated ofloxacin solution.

[0079] S42: Place the activated salbutamol obtained in step S2 into a solvent and stir to obtain an activated salbutamol solution;

[0080] S43: Mix the activated ofloxacin solution and the activated salbutamol solution, stir to obtain a mixed solution, and then immerse the activated silicone endotracheal tube in the mixed solution to obtain a highly effective antibacterial endotracheal tube.

[0081] As an optional embodiment of the present invention, the solvents in steps S41 and S42 include one or more of dimethyl sulfoxide, dichloromethane, and acetone.

[0082] And / or, step S43 includes: mixing activated ofloxacin solution and activated salbutamol solution at 40-60℃ and stirring for 4-6 hours to obtain a mixed solution; immersing the activated silicone endotracheal tube in the mixed solution for 5-10 minutes; slowly removing it and placing it in a sealed container with a humidity of 80-100%; drying it at 50-70℃ for 25-35 minutes; repeating this process 2-4 times; then removing the silicone endotracheal tube and placing it in a sealed container with a humidity of 80-100%; and placing it at 45-55℃ for 15-24 hours to obtain a highly effective antibacterial endotracheal tube.

[0083] According to a second aspect of the present invention, a highly efficient antibacterial endotracheal tube is prepared by a method described above.

[0084] The present invention will now be described in further detail with reference to specific embodiments and comparative examples.

[0085] The chemical reagents and silicone endotracheal tubes used in this invention are all commercially available products.

[0086] Example 1

[0087] S1: Ofloxacin is placed in a first activating agent for a first activation treatment to obtain activated ofloxacin, which contains an amide group.

[0088] S11: Place ofloxacin in dichloromethane and stir to obtain ofloxacin solution;

[0089] S12: Diphenylmethane diisocyanate is placed in dichloromethane and stirred to obtain a first activator solution;

[0090] S13: At a temperature of 40℃, the first activator solution is added dropwise to the ofloxacin solution at a dropping rate of 2mL / min. After the addition is completed, the mixture is stirred for 20h. Then, water is added to the reaction solution, and the solid mixture is filtered and washed with water 1-3 times. Purification is carried out by recrystallization and then dried at 60℃ for 48h to obtain activated ofloxacin.

[0091] The molar ratio of ofloxacin in the ofloxacin solution to diphenylmethane diisocyanate in the first activator solution is 1:2.

[0092] S2: Salbutamol is placed in a second activator for a second activation treatment to obtain activated salbutamol, which contains an ether group.

[0093] S21: Salbutamol is placed in dichloromethane and stirred to obtain a salbutamol solution;

[0094] S22: Ethylene oxide is placed in dichloromethane and stirred to obtain a second activator solution;

[0095] S23: Under the conditions of pH 8 and reaction temperature of 40℃, the second activator solution is added dropwise to the salbutamol solution at a dropping rate of 2mL / min. After the addition is completed, the mixture is stirred for 20h. Then water is added to the reaction solution, the solid mixture is filtered, washed with water 1-3 times, purified by recrystallization, and dried at 60℃ for 48h to obtain activated salbutamol.

[0096] The molar ratio of salbutamol in the salbutamol solution to ethylene oxide in the second activator solution is 1:2.

[0097] S3: The silicone endotracheal cannula is subjected to oxygen plasma treatment to obtain an activated silicone endotracheal cannula. The surface of the activated silicone endotracheal cannula contains silanol groups.

[0098] The parameters are as follows: power 90W, airflow rate 110mL / min, air pressure 70Pa, and etching time 60s.

[0099] S4: Activated ofloxacin and activated salbutamol are grafted onto the surface of an activated silicone endotracheal tube to obtain a highly effective antibacterial endotracheal tube.

[0100] S41: Place the activated ofloxacin obtained in step S1 into dimethyl sulfoxide and stir to obtain an activated ofloxacin solution.

[0101] S42: Place the activated salbutamol obtained in step S2 into the solvent dimethyl sulfoxide and stir to obtain an activated salbutamol solution.

[0102] S43: Mix the activated ofloxacin solution and the activated salbutamol solution at 50°C and stir for 6 hours to obtain a mixed solution. Then, immerse the activated silicone endotracheal tube in the mixed solution for 10 minutes, slowly remove it and place it in a sealed container with 100% humidity. Dry it at 50°C for 30 minutes. Repeat this process 2-4 times. Then, remove the silicone endotracheal tube and place it in a sealed container with 100% humidity. After placing it at 50°C for 24 hours, a highly effective antibacterial endotracheal tube is obtained.

[0103] Example 2

[0104] S1: Ofloxacin is placed in a first activating agent for a first activation treatment to obtain activated ofloxacin, which contains an amide group.

[0105] S11: Place ofloxacin in dimethyl sulfoxide and stir to obtain ofloxacin solution;

[0106] S12: Isophorone diisocyanate is placed in dimethyl sulfoxide solvent and stirred to obtain the first activator solution;

[0107] S13: At a temperature of 30℃, the first activator solution is added dropwise to the ofloxacin solution at a dropping rate of 2mL / min. After the addition is completed, the mixture is stirred for 24h. Then, water is added to the reaction solution, and the solid mixture is filtered and washed with water 1-3 times. Purification is carried out by recrystallization and then dried at 60℃ for 48h to obtain activated ofloxacin.

[0108] The molar ratio of ofloxacin in the ofloxacin solution to isophorone diisocyanate in the first activator solution is 1:1.

[0109] S2: Salbutamol is placed in a second activator for a second activation treatment to obtain activated salbutamol, which contains an ether group.

[0110] S21: Salbutamol is placed in dichloromethane and stirred to obtain a salbutamol solution;

[0111] S22: Propylene oxide is placed in dichloromethane solvent and stirred to obtain a second activator solution;

[0112] S23: Under the conditions of pH 9 and reaction temperature of 50℃, the second activator solution is added dropwise to the salbutamol solution at a dropping rate of 2mL / min. After the addition is completed, the mixture is stirred for 24h. Then, water is added to the reaction solution, and the solid mixture is filtered and washed with water 1-3 times. Purification is carried out by recrystallization and dried at 60℃ for 48h to obtain activated salbutamol.

[0113] The molar ratio of salbutamol in the salbutamol solution to propylene oxide in the second activator solution is 1:1.

[0114] S3: The silicone endotracheal tube is subjected to oxygen plasma treatment to obtain an activated silicone endotracheal tube. The surface of the activated silicone endotracheal tube contains silanol groups.

[0115] The parameters are as follows: power 90W, airflow rate 110mL / min, air pressure 70Pa, and etching time 60s.

[0116] S4: Activated ofloxacin and activated salbutamol are grafted onto the surface of an activated silicone endotracheal tube to obtain a highly effective antibacterial endotracheal tube.

[0117] S41: Place the activated ofloxacin obtained in step S1 into dimethyl sulfoxide and stir to obtain an activated ofloxacin solution.

[0118] S42: Place the activated salbutamol obtained in step S2 into dimethyl sulfoxide and stir to obtain an activated salbutamol solution;

[0119] S43: Mix the activated ofloxacin solution and the activated salbutamol solution at 60°C and stir for 6 hours to obtain a mixed solution. Then, immerse the activated silicone endotracheal tube in the mixed solution for 10 minutes, slowly remove it and place it in a sealed container with 100% humidity. Dry it at 50°C for 35 minutes. Repeat this process 2-4 times. Then, remove the silicone endotracheal tube and place it in a sealed container with 100% humidity. Place it at 55°C for 24 hours to obtain a highly effective antibacterial endotracheal tube.

[0120] Example 3

[0121] S1: Ofloxacin is placed in a first activating agent for a first activation treatment to obtain activated ofloxacin, which contains an amide group.

[0122] S11: Place ofloxacin in acetone and stir to obtain ofloxacin solution;

[0123] S12: Naphthalene diisocyanate is placed in acetone and stirred to obtain the first activator solution;

[0124] S13: At a temperature of 50℃, the first activator solution is added dropwise to the ofloxacin solution at a dropping rate of 2mL / min. After the addition is complete, the mixture is stirred for 10h. Then, water is added to the reaction solution, and the solid mixture is filtered and washed with water 1-3 times. Purification is carried out by recrystallization and then dried at 60℃ for 48h to obtain activated ofloxacin.

[0125] The molar ratio of ofloxacin in the ofloxacin solution to naphthalene diisocyanate in the first activator solution is 1:3.

[0126] S2: Salbutamol is placed in a second activator for a second activation treatment to obtain activated salbutamol, which contains an ether group.

[0127] S21: Salbutamol is placed in tetrahydrofuran and stirred to obtain a salbutamol solution;

[0128] S22: Epichlorohydrin is placed in dichloromethane and stirred to obtain a second activator solution;

[0129] S23: Under the conditions of pH 9 and reaction temperature of 30℃, the second activator solution is added dropwise to the salbutamol solution at a dropping rate of 2mL / min. After the addition is completed, the mixture is stirred for 24h. Then, water is added to the reaction solution, and the solid mixture is filtered and washed with water 1-3 times. Purification is carried out by recrystallization and dried at 60℃ for 48h to obtain activated salbutamol.

[0130] The molar ratio of salbutamol in the salbutamol solution to epichlorohydrin in the second activator solution is 1:3.

[0131] S3: The silicone endotracheal tube is subjected to oxygen plasma treatment to obtain an activated silicone endotracheal tube. The surface of the activated silicone endotracheal tube contains silanol groups.

[0132] The parameters are as follows: power 90W, airflow rate 110mL / min, air pressure 70Pa, and etching time 60s.

[0133] S4: Activated ofloxacin and activated salbutamol are grafted onto the surface of an activated silicone endotracheal tube to obtain a highly effective antibacterial endotracheal tube.

[0134] S41: Place the activated ofloxacin obtained in step S1 into dimethyl sulfoxide and stir to obtain an activated ofloxacin solution.

[0135] S42: Place the activated salbutamol obtained in step S2 into dimethyl sulfoxide and stir to obtain an activated salbutamol solution;

[0136] S43: Mix the activated ofloxacin solution and the activated salbutamol solution at 60°C and stir for 6 hours to obtain a mixed solution. Then, immerse the activated silicone endotracheal tube in the mixed solution for 10 minutes, slowly remove it and place it in a sealed container with 100% humidity. Dry it at 50°C for 35 minutes. Repeat this process 2-4 times. Then, remove the silicone endotracheal tube and place it in a sealed container with 100% humidity. Place it at 55°C for 24 hours to obtain a highly effective antibacterial endotracheal tube.

[0137] Comparative Example 1

[0138] The difference between this comparative example and Example 1 is that ofloxacin is replaced with a quaternary ammonium salt organic antibacterial agent, benzbromarone. The remaining steps and technical parameters are the same as in Example 1.

[0139] Performance testing

[0140] The antibacterial properties of the prepared highly effective antibacterial endotracheal tube against Escherichia coli, Enterobacter faecalis, and Candida albicans were tested according to standard ISO22196-2011.

[0141] Results data

[0142] Table 1: Antibacterial properties of the highly effective antibacterial endotracheal tubes prepared in Examples 1-3

[0143]

[0144] As shown in Table 1, compared with Example 1, Comparative Example 1 replaced ofloxacin with a quaternary ammonium salt organic antibacterial agent, benzbromarone. After benzbromarone was activated with diphenylmethane diisocyanate, an activated product with a carbamate group was generated. In step S4, the activated product with a carbamate group may react with the amino group in salbutamol to generate an amide bond, thereby affecting the efficacy of salbutamol. This not only reduced the antibacterial activity but also affected the tracheal adaptability.

[0145] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a highly efficient antibacterial endotracheal tube, characterized in that, Includes the following steps: S1: Ofloxacin is placed in a first activator for a first activation treatment to obtain activated ofloxacin, which contains an amide group; The first activation process includes: S11: Place ofloxacin in a solvent and stir to obtain ofloxacin solution; S12: Place the first activator in a solvent and stir to obtain a first activator solution; S13: Add the first activator solution dropwise to the ofloxacin solution, stir, then add water to the reaction solution, filter, take the solid mixture, wash, purify, and dry to obtain activated ofloxacin; S2: Salbutamol is placed in a second activator for a second activation treatment to obtain activated salbutamol, which contains an ether group; The second activation treatment includes: S21: Place salbutamol in a solvent and stir to obtain a salbutamol solution; S22: Place the second activator in a solvent and stir to obtain a solution of the second activator; S23: Add the second activator solution dropwise to the salbutamol solution, stir, then add water to the reaction solution, filter, take the solid mixture, wash, purify, and dry to obtain activated salbutamol; S3: Perform a third activation treatment on the silicone endotracheal tube to obtain an activated silicone endotracheal tube. The surface of the activated silicone endotracheal tube contains silanol groups. S4: Activated ofloxacin and activated salbutamol are grafted onto the surface of activated silicone endotracheal tubes to obtain highly effective antibacterial endotracheal tubes. The first activator includes one or more of diphenylmethane diisocyanate, isophorone diisocyanate, hexamethylene diisocyanate, and naphthalene diisocyanate; The second activator includes one or more of the following: ethylene oxide, propylene oxide, epichlorohydrin, phenylene oxide, and 1,2-epoxybutane.

2. The method for preparing a highly efficient antibacterial endotracheal tube according to claim 1, characterized in that, The solvents used in steps S11 and S12 include one or more of dichloromethane, acetone, and dimethyl sulfoxide. And / or, the molar ratio of ofloxacin in the ofloxacin solution to the first activator in the first activator solution is 1:(1-3). And / or, in step S13, the reaction conditions include: a reaction temperature of 30-50℃, a dropping rate of (1-2) mL / min, and a reaction time of 10-24 h after the dropping is completed; And / or, add water to the reaction solution to precipitate the reactants, filter and take the solid mixture, wash with water 1-3 times, purify by recrystallization, and dry at 50-80℃ for 24-48h.

3. The method for preparing a highly efficient antibacterial endotracheal tube according to claim 1, characterized in that, The solvents used in steps S21 and S22 include one or more of dichloromethane, tetrahydrofuran, and ethyl acetate; And / or, the molar ratio of salbutamol in the salbutamol solution to the second activator in the second activator solution is 1:(1-3); And / or, in step S23, the reaction conditions include: pH 8-9, reaction temperature 30-50℃, dropping rate (1-2) mL / min, and reaction time 10-24 h after dropping is completed; And / or, water is added to the reaction solution to precipitate the reactants. After filtration, the solid mixture is washed with water 1-3 times. Purification is carried out by recrystallization and drying at 50-80℃ for 24-48 hours.

4. The method for preparing a highly efficient antibacterial endotracheal tube according to claim 1, characterized in that, In step S3, the third activation treatment is oxygen plasma treatment, and the oxygen plasma treatment conditions are: power 70-90W, gas flow rate 90-110mL / min, gas pressure 50-70Pa, and etching time 30-60s.

5. The method for preparing a highly efficient antibacterial endotracheal tube according to claim 1, characterized in that, Step S4 specifically includes the following steps: S41: Place the activated ofloxacin obtained in step S1 into a solvent and stir to obtain an activated ofloxacin solution. S42: Place the activated salbutamol obtained in step S2 into a solvent and stir to obtain an activated salbutamol solution; S43: Mix the activated ofloxacin solution and the activated salbutamol solution, stir to obtain a mixed solution, and then immerse the activated silicone endotracheal tube in the mixed solution to obtain a highly effective antibacterial endotracheal tube.

6. The method for preparing a highly efficient antibacterial endotracheal tube according to claim 5, characterized in that, The solvents used in steps S41 and S42 include one or more of dimethyl sulfoxide, dichloromethane, and acetone. And / or, step S43 includes: mixing activated ofloxacin solution and activated salbutamol solution at 40-60℃ and stirring for 4-6 hours to obtain a mixed solution; immersing the activated silicone endotracheal tube in the mixed solution for 5-10 minutes; slowly removing it and placing it in a sealed container with 80-100% humidity; drying it at 50-70℃ for 25-35 minutes; repeating this process 2-4 times; then removing the silicone endotracheal tube and placing it in a sealed container with 80-100% humidity; and placing it at 45-55℃ for 15-24 hours to obtain a highly effective antibacterial endotracheal tube.

7. A highly efficient antibacterial endotracheal tube prepared by the preparation method of the highly efficient antibacterial endotracheal tube as described in any one of claims 1-6.

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