Efficient antibacterial trachea cannula and preparation method thereof

Abstract

The invention provides an efficient antibacterial trachea cannula and a preparation method thereof, and relates to the technical field of medical implant materials.The preparation method comprises the following steps that S1, ofloxacin is placed in a first activating agent to be subjected to first activating treatment, activated ofloxacin is obtained, and the activated ofloxacin contains amido; s2, salbutamol is placed in a second activating agent to be subjected to second activating treatment, activated salbutamol is obtained, and the activated salbutamol contains ether groups; s3, the silica gel trachea cannula is subjected to third activation treatment, an activated silica gel trachea cannula is obtained, and the surface of the activated silica gel trachea cannula contains silanol groups; s4, the activated ofloxacin and the activated salbutamol are grafted to the surface of the activated silica gel trachea cannula, and the efficient antibacterial trachea cannula is obtained. According to the invention, ofloxacin and salbutamol are respectively activated, so that the ofloxacin and the salbutamol are connected to the surface of the silica gel trachea cannula, and the trachea cannula has efficient antibacterial property and tracheal adaptability.

Description

Technical Field

[0001] The present invention relates to the technical field of medical implant materials, and particularly to an endotracheal tube with high antibacterial efficiency and its preparation method. Background Art

[0002] Silicone, as a high-performance medical material, is widely used in the medical field due to its unique physical and chemical properties and biocompatibility, and shows significant advantages especially in the manufacture of endotracheal tubes. Silicone endotracheal tubes not only have good elasticity and softness, can conform to the airway structure, reduce discomfort and injury during intubation, but also ensure the safety and comfort of patients because of their stable chemical properties and not being prone to cause allergic or rejection reactions. However, despite many advances in the design and material selection of silicone endotracheal tubes, there are still some challenges in clinical applications, and the most prominent problem is the lack of antibacterial performance and the possible respiratory complications after intubation.

[0003] As a necessary first-aid and surgical assistance means, endotracheal intubation artificially establishes an airway passage to ensure the patency of the patient's breathing. However, this invasive operation inevitably breaks the natural defense barrier of the airway, allowing external bacteria, viruses and other microorganisms to enter the airway, increasing the risk of infection. Especially when the endotracheal tube is indwelling for a long time, the microenvironment in the airway changes, and bacteria are more likely to colonize and multiply on the surface of the intubation and inside the airway, leading to the occurrence of respiratory tract infections. Although the surface of the silicone endotracheal tube is smooth, which is conducive to reducing bacterial adhesion, it does not have the ability to actively sterilize or inhibit bacteria, which to a certain extent limits its effect in preventing infections.

[0004] More seriously, endotracheal intubation also interferes with the patient's cough reflex, which is an important mechanism for the human body to clear respiratory secretions and foreign bodies. Normally, coughing can effectively expel sputum, food residues and other substances out of the body, maintaining the cleanliness and patency of the respiratory tract. However, after intubation, due to the inhibition of the cough reflex, sputum and other excreta cannot be effectively coughed out and are prone to accumulate inside the trachea and the intubation. Over time, these excreta gradually dry and solidify to form blockages such as sputum crusts and mucus plugs, which not only hinder the patency of the airway, but also may become a breeding ground for bacteria, further increasing the risk of respiratory tract infections.

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

[0006] The purpose of the present invention is to provide an endotracheal tube with high antibacterial efficiency and its preparation method. By respectively activating ofloxacin and salbutamol and connecting them to the surface of the silicone endotracheal tube, the endotracheal tube has high antibacterial property and tracheal adaptability.

[0007] To achieve the above object, the present invention adopts the following technical solutions:

[0008] The present invention provides a preparation method of a tracheal intubation with high antibacterial efficiency, comprising the following steps:

[0009] S1: Ofloxacin is subjected to a first activation treatment in a first activator to obtain activated ofloxacin, and the activated ofloxacin contains an amide group;

[0010] S2: Salbutamol is subjected to a second activation treatment in a second activator to obtain activated salbutamol, and the activated salbutamol contains an ether group;

[0011] S3: The silicone tracheal intubation is subjected to a third activation treatment to obtain an activated silicone tracheal intubation, and the surface of the activated silicone tracheal intubation contains silanol groups;

[0012] S4: The activated ofloxacin and the activated salbutamol are grafted onto the surface of the activated silicone tracheal intubation to obtain a tracheal intubation with high antibacterial efficiency.

[0013] Further, on the basis of the above technical solution, the first activator includes: one or more of 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, styrene oxide, and 1,2-epoxybutane.

[0015] Further, on the basis of the above technical solution, in step S1, the first activation treatment includes:

[0016] S11: Ofloxacin is placed in a solvent and stirred to obtain an ofloxacin solution;

[0017] S12: The first activator is placed in a solvent and stirred to obtain a first activator solution;

[0018] S13: The first activator solution is added dropwise to the ofloxacin solution, stirred, water is added to the reaction solution, the solid mixture is taken after filtration, washed, purified, and dried to obtain activated ofloxacin.

[0019] Further, on the basis of the above technical solution, the solvents in steps S11 and S12 both 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: the reaction temperature is 30 - 50°C, the dropping rate is (1 - 2) mL / min, and the reaction time after dropping is completed is 10 - 24 h;

[0022] And / or, water is added to the reaction solution to precipitate the reactants. After filtration, the solid mixture is taken, washed with water 1 - 3 times, purified by recrystallization, and dried at 50 - 80°C for 24 - 48 h.

[0023] Furthermore, on the basis of 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 second activator solution;

[0026] S23: Drop the second activator solution into the salbutamol solution, stir, then add water to the reaction solution. After filtration, the solid mixture is taken, washed, purified, and dried to obtain activated salbutamol.

[0027] Furthermore, on the basis of the above technical solution, the solvents in steps S21 and S22 both 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: the pH is 8 - 9, the reaction temperature is 30 - 50°C, the dropping rate is (1 - 2) mL / min, and the reaction time after dropping is completed is 10 - 24 h;

[0030] And / or, adding water to the reaction solution is used to precipitate the reactants. After filtration, the solid mixture is taken, washed with water 1 - 3 times, purified by recrystallization, and dried at 50 - 80°C for 24 - 48 h.

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

[0032] Furthermore, on the basis of the above technical solution, in step S4, it specifically includes the following steps:

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

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

[0035] S43: After mixing the activated ofloxacin solution and the activated salbutamol solution, stir to obtain a mixed solution, and then immerse the activated silica gel tracheal intubation in the mixed solution to obtain a highly antibacterial tracheal intubation.

[0036] Further, on the basis of 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 the activated ofloxacin solution and the activated salbutamol solution at 40 - 60 °C, then stirring for 4 - 6 h to obtain a mixed solution, then immersing the activated silica gel tracheal intubation in the mixed solution for 5 - 10 min, slowly taking it out and placing it in a sealed container with a humidity of 80 - 100%, drying at a temperature of 50 - 70 °C for 25 - 35 min, repeating 2 - 4 times, then taking out the silica gel tracheal intubation and placing it in a sealed container with a humidity of 80 - 100%, and placing it at 45 - 55 °C for 15 - 24 h to obtain a highly antibacterial tracheal intubation.

[0038] The present invention also provides a highly antibacterial tracheal intubation prepared by the preparation method of the highly antibacterial tracheal intubation as described above.

[0039] A highly antibacterial tracheal intubation and its preparation method provided by the present invention have the following beneficial effects:

[0040] The present invention respectively activates ofloxacin and salbutamol: on the molecular structure of ofloxacin, an amide group is grafted through a specific chemical reaction. This group not only enhances the activity of ofloxacin but also provides the possibility for its subsequent immobilization. At the same time, salbutamol also undergoes activation treatment, and an ether group is grafted onto its molecule. This group also provides conditions for its binding to the surface of silica gel. After the preparatory work is completed, the surface of the silica gel tracheal intubation is also activated, making its surface rich in silanol groups, providing reaction sites for the immobilization of ofloxacin and salbutamol. In the design of the present invention, the amide group on ofloxacin and the ether group on salbutamol both have good stability, and unnecessary chemical reactions do not occur between them, maintaining their respective chemical activities. In addition, ofloxacin and salbutamol are two different drugs, and there are obvious differences in their molecular structures, so they do not react with each other under normal conditions. This feature is particularly important in the application of the present invention because it ensures that when ofloxacin and salbutamol react with the silanol groups on the silica gel tracheal intubation, no cross-linking reaction occurs, thus avoiding unnecessary structural changes and functional losses. Therefore, when ofloxacin and salbutamol are respectively immobilized on the surface of the silica gel tracheal intubation, their amide groups and ether groups can be safely allowed to react with the silanol groups to form stable chemical bonds. This not only realizes the effective immobilization of the drugs but also maintains the activity of the drugs, providing the functions of high-efficiency antibacterial and tracheal adaptability for the tracheal intubation, while also ensuring the safety and reliability of the tracheal intubation. Detailed implementation mode

[0041] To make the objectives, technical solutions, and advantages of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Those skilled in the art should understand that the embodiments are only for helping to understand the present invention and should not be regarded as specific limitations on the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present invention. The process parameters without specific conditions noted in the following embodiments are usually in accordance with conventional conditions.

[0042] In the ranges disclosed in the present invention, the endpoints and any values of the ranges are not limited to the precise ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values and individual point values of each range, and between individual point values, they can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed in the present invention.

[0043] According to the first aspect of the present invention, there is provided a method for preparing a tracheal intubation with high-efficiency antibacterial properties, including the following steps:

[0044] S1: Subject ofloxacin to a first activation treatment in a first activator to obtain activated ofloxacin, and the activated ofloxacin contains an amide group;

[0045] S2: Subject salbutamol to a second activation treatment in a second activator to obtain activated salbutamol, and the activated salbutamol contains an ether group;

[0046] S3: Subject a silicone tracheal intubation to a third activation treatment to obtain an activated silicone tracheal intubation, and the surface of the activated silicone tracheal intubation contains silanol groups;

[0047] S4: Graft the activated ofloxacin and the activated salbutamol onto the surface of the activated silicone tracheal intubation to obtain a tracheal intubation with high antibacterial efficiency.

[0048] Specifically, in the present invention, ofloxacin and salbutamol are respectively subjected to activation treatments: in the molecular structure of ofloxacin, an amide group is grafted through a specific chemical reaction. This group not only enhances the activity of ofloxacin but also provides the possibility for its subsequent fixation. At the same time, salbutamol also undergoes an activation treatment, and an ether group is grafted onto its molecule. This group also provides conditions for its binding to the silicone surface. After the preparatory work is completed, the surface of the silicone tracheal intubation also undergoes an activation treatment, making its surface rich in silanol groups, providing reaction sites for the fixation of ofloxacin and salbutamol. In the design of the present invention, the amide group on ofloxacin and the ether group on salbutamol both have good stability, and they will not undergo unnecessary chemical reactions with each other, maintaining their respective chemical activities. In addition, ofloxacin and salbutamol are two different drugs, and they have obvious differences in molecular structure. Therefore, they will not react with each other under normal conditions. This feature is particularly important in the application of the present invention because it ensures that when ofloxacin and salbutamol react with the silanol groups on the silicone tracheal intubation, no cross-linking reaction will occur, thus avoiding unnecessary structural changes and functional losses. Therefore, when ofloxacin and salbutamol are respectively fixed on the surface of the silicone tracheal intubation, it is possible to safely allow their amide groups and ether groups to react with the silanol groups to form stable chemical bonds. This not only realizes the effective fixation of the drugs but also maintains the activity of the drugs, providing the tracheal intubation with functions of high antibacterial efficiency and tracheal adaptability, while also ensuring the safety and reliability of the tracheal intubation.

[0049] As an optional implementation manner 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 the quinolone ring structure in the ofloxacin molecule are the key points. They tightly bind to the A subunit of bacterial DNA gyrase, effectively blocking the normal replication and transcription processes of bacterial DNA. This binding not only prevents the unwinding and re-winding of bacterial DNA but also causes the breakage of bacterial DNA strands, thereby inhibiting the growth and reproduction of bacteria. To protect the unique functional groups with antibacterial properties in ofloxacin, the present invention uses isocyanate activators to activate ofloxacin; during the process of using isocyanate compounds for the activation treatment of ofloxacin, their reactions mainly focus on the coupling with other specific functional groups in the ofloxacin molecule, and will not directly act on the fluorine atom and the quinolone ring structure in ofloxacin. This is because the reaction activity of isocyanate compounds mainly focuses on their isocyanate groups, and this group tends to react with the carboxyl functional group in the ofloxacin molecule to form stable chemical bonds. The fluorine atom and the quinolone ring structure in ofloxacin will not be affected by isocyanate compounds.

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

[0052] In addition, isocyanate activators also have good biocompatibility and low toxicity. The by-products released during the activation treatment with isocyanate activators are usually harmless to the human body, and the activated ofloxacin molecules can also maintain stable chemical properties in the organism, without triggering unnecessary biological reactions or toxic effects.

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

[0054] Specifically, salbutamol is a commonly used β2 receptor agonist, and its surface contains functional groups such as alcohol groups and amine groups. The amine group on the surface of salbutamol is the key to its pharmacological effect. It can bind to the β2 adrenergic receptor, activate this receptor, cause the relaxation of bronchial smooth muscle, relieve bronchospasm, and thus relieve symptoms such as dyspnea during asthma attacks.

[0055] In the present invention, salbutamol is activated by an epoxy compound because in the salbutamol molecule, the epoxy compound will preferentially react with the alcoholic hydroxyl group of salbutamol rather than with its amino group. This selectivity stems from the kinetic advantage of the reaction between the alcoholic hydroxyl group and the epoxy group, as well as the relatively strong nucleophilicity of the amino group itself, which makes the amino group not easily react directly with the epoxy compound under general conditions. After the epoxy compound reacts with the alcoholic hydroxyl group of salbutamol, a corresponding ether compound is formed. This chemical reaction not only stabilizes the structure of salbutamol but also avoids interfering with the amino group part that is crucial for its drug efficacy. The amino group is the key functional group for salbutamol to exert its β2-adrenergic receptor agonist effect, and its integrity is crucial for maintaining the biological activity of the drug. Therefore, by selectively reacting with the alcoholic hydroxyl group, the present invention ensures that the core pharmacodynamic structure of salbutamol is completely retained during the activation process. Further, the ether bond formed by the reaction of the epoxy compound with the alcoholic hydroxyl group on the surface of salbutamol provides a reliable fixation point for salbutamol.

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

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

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

[0059] S13: Drop the first activator solution into the ofloxacin solution, stir, then add water to the reaction solution, filter to obtain a solid mixture, wash, purify, and dry it to obtain activated ofloxacin.

[0060] As an alternative embodiment of the present invention, the solvents in steps S11 and S12 both 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, the present invention defines the molar ratio of ofloxacin in the ofloxacin solution to isocyanate in the isocyanate activator solution as 1:(1 - 3). The purpose is to ensure that the amide groups on the ofloxacin molecules can graft with isocyanate to an appropriate extent. This not only retains the original pharmacological activity of ofloxacin but also significantly enhances the binding ability of ofloxacin to the silicone tracheal intubation. This enhanced binding force is of great significance for achieving controlled release of drugs, targeted drug delivery, and improving the stability and bioavailability of drugs in the body. In addition, unnecessary side reactions such as excessive cross-linking reactions and hydrolysis reactions are reduced. These side reactions may reduce the purity of the target product and even produce toxic and harmful substances.

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

[0064] And / or, water is added to the reaction solution to precipitate the reactants. After filtration, the solid mixture is taken, washed 1 - 3 times with water, and purified by recrystallization, and dried at 50 - 80°C for 24 - 48 h.

[0065] As an alternative embodiment of the present invention, in step S2, the second activation treatment includes:

[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 second activator solution;

[0068] S23: Drop the second activator solution into the salbutamol solution, stir, then add water to the reaction solution. After filtration, take the solid mixture, wash, purify, and dry to obtain activated salbutamol.

[0069] As an alternative embodiment of the present invention, the solvents in steps S21 and S22 both 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, the present invention defines the molar ratio of salbutamol in the salbutamol solution to the epoxy compound in the epoxy compound activator solution as 1:(1 - 3). The purpose is to precisely control the reaction process, ensure an efficient and controllable grafting reaction between the alcohol hydroxyl group in the salbutamol molecule and the epoxy compound, thereby enhancing its binding force with the silicone tracheal intubation while retaining the original pharmacological activity of salbutamol, reducing unnecessary side reactions, and improving the purity and stability of the target product.

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

[0073] And / or, adding water to the reaction solution is used to precipitate the reactants. After filtration, the solid mixture is taken and washed with water 1 - 3 times. The purification is carried out by recrystallization purification and dried at 50 - 80 °C for 24 - 48 h.

[0074] As an alternative 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 - 90 W, gas flow rate 90 - 110 mL / min, air pressure 50 - 70 Pa, and etching time 30 - 60 s.

[0076] Specifically, the present invention activates the silicone tracheal intubation through oxygen plasma, increasing a large number of active silanol groups on its surface. The introduction of active silanol groups provides abundant reaction sites for subsequent grafting reactions. This enables the surface of the silicone tracheal intubation to more easily undergo chemical bonding with the amide group on ofloxacin and the ether group on salbutamol. The carbonyl oxygen atom in the amide group can form a hydrogen bond with the hydrogen atom in the silanol group, and further form a covalent bond through a condensation reaction, thereby firmly fixing ofloxacin on the surface of the silicone tracheal intubation; the oxygen atom in the ether group on salbutamol can form a hydrogen bond with the hydrogen atom in the silanol group, and then form a siloxane bond through the condensation reaction between silanol groups, thereby fixing salbutamol on the surface of the silicone tracheal intubation; achieving the immobilization of ofloxacin and salbutamol, targeted drug delivery, or improvement of biocompatibility, and further enhancing the high - efficiency antibacterial property and tracheal adaptability of the tracheal intubation. Moreover, the presence of active silanol groups also enhances the hydrophilicity of the surface of the silicone tracheal intubation. The improvement of hydrophilicity helps to reduce the attachment and growth of bacteria and other microorganisms on the silicone surface, thereby reducing the risk of infection.

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

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

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

[0080] S43: After mixing the activated ofloxacin solution and the activated salbutamol solution, stir to obtain a mixed solution, and then immerse the activated silica gel tracheal intubation in the mixed solution to obtain a highly antibacterial tracheal intubation.

[0081] As an optional implementation mode of the present invention, the solvents in step S41 and step S42 both include one or more of dimethyl sulfoxide, dichloromethane, and acetone;

[0082] And / or, step S43 includes: mixing the activated ofloxacin solution and the activated salbutamol solution at 40 - 60 °C, stirring for 4 - 6 h to obtain a mixed solution, then immersing the activated silica gel tracheal intubation in the mixed solution for 5 - 10 min, slowly taking it out and placing it in a sealed container with a humidity of 80 - 100%, drying at a temperature of 50 - 70 °C for 25 - 35 min, repeating 2 - 4 times, then taking out the silica gel tracheal intubation and placing it in a sealed container with a humidity of 80 - 100%, and placing it at 45 - 55 °C for 15 - 24 h to obtain a highly antibacterial tracheal intubation.

[0083] According to the second aspect of the present invention, a highly antibacterial tracheal intubation prepared by the preparation method of the highly antibacterial tracheal intubation as described above is provided.

[0084] The present invention will be further described in detail below with specific examples and comparative examples.

[0085] The chemical reagents and silica gel tracheal intubations used in the present invention are all commercially available products.

[0086] Example 1

[0087] S1: Perform a first activation treatment on ofloxacin in a first activator to obtain activated ofloxacin, and the activated ofloxacin contains an amide group:

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

[0089] S12: Place diphenylmethane diisocyanate in dichloromethane and stir to obtain a first activator solution;

[0090] S13: At a temperature of 40 °C, the first activator solution was added dropwise to the ofloxacin solution at a dropping rate of 2 mL / min. After the addition was completed, the mixture was stirred and reacted for 20 h. Then water was added to the reaction solution. After filtration, the solid mixture was taken and washed with water 1 - 3 times. Purification was carried out by recrystallization and drying was performed at 60 °C for 48 h to obtain activated ofloxacin;

[0091] Among them, the molar ratio of ofloxacin in the ofloxacin solution to diphenylmethane diisocyanate in the first activator solution was 1:2.

[0092] S2: Salbutamol was subjected to a second activation treatment in a second activator to obtain activated salbutamol, and the activated salbutamol contained an ether group:

[0093] S21: Salbutamol was stirred in dichloromethane to obtain a salbutamol solution;

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

[0095] S23: Under the conditions of pH = 8 and a reaction temperature of 40 °C, the second activator solution was added dropwise to the salbutamol solution at a dropping rate of 2 mL / min. After the addition was completed, the mixture was stirred and reacted for 20 h. Then water was added to the reaction solution. After filtration, the solid mixture was taken and washed with water 1 - 3 times. Purification was carried out by recrystallization and drying was performed at 60 °C for 48 h to obtain activated salbutamol;

[0096] Among them, the molar ratio of salbutamol in the salbutamol solution to ethylene oxide in the second activator solution was 1:2.

[0097] S3: The silicone tracheal intubation was treated with oxygen plasma to obtain an activated silicone tracheal intubation, and the surface of the activated silicone tracheal intubation contained silanol groups:

[0098] Among them, the power was 90 W, the gas flow rate was 110 mL / min, the air pressure was 70 Pa, and the etching time was 60 s.

[0099] S4: The activated ofloxacin and the activated salbutamol were grafted onto the surface of the activated silicone tracheal intubation to obtain a highly antibacterial tracheal intubation:

[0100] S41: The activated ofloxacin obtained in step S1 was placed in dimethyl sulfoxide and stirred to obtain an activated ofloxacin solution;

[0101] S42: The activated salbutamol obtained in step S2 was placed in the solvent dimethyl sulfoxide and stirred to obtain an activated salbutamol solution;

[0102] S43: After mixing the activated ofloxacin solution and the activated salbutamol solution at 50°C, stir for 6 h to obtain a mixed solution. Then immerse the activated silica tracheal intubation into the mixed solution for 10 min, slowly take it out and place it in a sealed container with a humidity of 100%, dry it at 50°C for 30 min, repeat 2 - 4 times, and then take out the silica tracheal intubation and place it in a sealed container with a humidity of 100%. After placing it at 50°C for 24 h, a highly antibacterial tracheal intubation is obtained.

[0103] Example 2

[0104] S1: Perform a first activation treatment on ofloxacin in a first activator to obtain activated ofloxacin, and the activated ofloxacin contains an amide group:

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

[0106] S12: Place isophorone diisocyanate in the solvent dimethyl sulfoxide and stir to obtain a first activator solution;

[0107] S13: At a temperature of 30°C, drop the first activator solution into the ofloxacin solution at a dropping rate of 2 mL / min. After the dropping is completed, stir and react for 24 h. Then add water to the reaction solution, filter to obtain a solid mixture, wash it with water 1 - 3 times, and use recrystallization purification for purification. Dry it at 60°C for 48 h to obtain activated ofloxacin;

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

[0109] S2: Perform a second activation treatment on salbutamol in a second activator to obtain activated salbutamol, and the activated salbutamol contains an ether group:

[0110] S21: Place salbutamol in dichloromethane and stir to obtain a salbutamol solution;

[0111] S22: Place propylene oxide in the solvent dichloromethane and stir to obtain a second activator solution;

[0112] S23: Under the conditions of pH 9 and a reaction temperature of 50°C, drop the second activator solution into the salbutamol solution at a dropping rate of 2 mL / min. After the dropping is completed, stir and react for 24 h. Then add water to the reaction solution, filter to obtain a solid mixture, wash it with water 1 - 3 times, and use recrystallization purification for purification. Dry it at 60°C for 48 h to obtain activated salbutamol;

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

[0114] S3: Perform oxygen plasma treatment on the silicone tracheal intubation to obtain an activated silicone tracheal intubation, and the surface of the activated silicone tracheal intubation contains silanol groups;

[0115] Among them, the power is 90W, the gas flow rate is 110mL / min, the air pressure is 70Pa, and the etching time is 60s.

[0116] S4: Graft the activated ofloxacin and the activated salbutamol onto the surface of the activated silicone tracheal intubation to obtain a highly antibacterial tracheal intubation:

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

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

[0119] S43: After mixing the activated ofloxacin solution and the activated salbutamol solution at 60°C, stir for 6h to obtain a mixed solution, then immerse the activated silicone tracheal intubation in the mixed solution for 10min, slowly take it out and place it in a sealed container with a humidity of 100%, dry it at 50°C for 35min, repeat 2 - 4 times, then take out the silicone tracheal intubation and place it in a sealed container with a humidity of 100%, and place it at 55°C for 24h to obtain a highly antibacterial tracheal intubation.

[0120] Example 3

[0121] S1: Perform the first activation treatment on ofloxacin in the first activator to obtain activated ofloxacin, and the activated ofloxacin contains amide groups:

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

[0123] S12: Place naphthalene diisocyanate in acetone and stir to obtain a first activator solution;

[0124] S13: At a temperature of 50°C, drop the first activator solution into the ofloxacin solution at a dropping rate of 2mL / min. After the dropping is completed, stir and react for 10h, then add water to the reaction solution, filter to obtain a solid mixture, wash it with water 1 - 3 times, and use recrystallization purification for purification. Dry it at 60°C for 48h to obtain activated ofloxacin;

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

[0126] S2: Subject salbutamol to a second activation treatment in a second activator to obtain activated salbutamol, and the activated salbutamol contains an ether group:

[0127] S21: Place salbutamol in tetrahydrofuran and stir to obtain a salbutamol solution;

[0128] S22: Place epichlorohydrin in dichloromethane and stir to obtain a second activator solution;

[0129] S23: Under the conditions of pH 9 and a reaction temperature of 30 °C, drop the second activator solution into the salbutamol solution at a dropping rate of 2 mL / min. After the dropping is completed, carry out a stirring reaction for 24 h. Then add water to the reaction solution, filter to obtain a solid mixture, wash it with water 1 - 3 times, and use recrystallization for purification. Dry it at 60 °C for 48 h to obtain activated salbutamol;

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

[0131] S3: Subject the silicone tracheal intubation to oxygen plasma treatment to obtain an activated silicone tracheal intubation, and the surface of the activated silicone tracheal intubation contains silanol groups;

[0132] Among them, the power is 90 W, the gas flow rate is 110 mL / min, the air pressure is 70 Pa, and the etching time is 60 s.

[0133] S4: Graft the activated ofloxacin and the activated salbutamol onto the surface of the activated silicone tracheal intubation to obtain a highly antibacterial tracheal intubation:

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

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

[0136] S43: After mixing the activated ofloxacin solution and the activated salbutamol solution at 60 °C, stir for 6 h to obtain a mixed solution. Then immerse the activated silicone tracheal intubation in the mixed solution for 10 min, slowly take it out and place it in a sealed container with a humidity of 100%, dry it at a temperature of 50 °C for 35 min, repeat 2 - 4 times, and then take out the silicone tracheal intubation and place it in a sealed container with a humidity of 100%. After placing it at 55 °C for 24 h, a highly antibacterial tracheal intubation is obtained.

[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, benzalkonium bromide, and the remaining steps and technical parameters are the same as those in Example 1.

[0139] Performance Test

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

[0141] Effect Data

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

[0143]

[0144] As can be seen from Table 1, compared with Example 1, in Comparative Example 1, since ofloxacin is replaced with a quaternary ammonium salt organic antibacterial agent, benzalkonium bromide, after benzalkonium bromide is activated with diphenylmethane diisocyanate, an activated product with a carbamate group is formed. In step S4, the activated product with a carbamate group may react with the amino group in salbutamol to form an amide bond, thus affecting the drug property of salbutamol, not only reducing the antibacterial property but also affecting the adaptability of the trachea.

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

Claims

1. A method for preparing a highly effective antibacterial endotracheal tube, characterized in that: The steps include: S1: placing ofloxacin in a first activating agent for a first activation treatment to obtain activated ofloxacin, wherein the activated ofloxacin contains an amide group; S2: placing the salbutamol in a second activating agent for a second activation treatment to obtain activated salbutamol, wherein the activated salbutamol contains an ether group; S3: performing a third activation treatment on the silicone endotracheal cannula to obtain an activated silicone endotracheal cannula, wherein the surface of the activated silicone endotracheal cannula contains silanol groups; S4: Activated ofloxacin and activated salbutamol were grafted onto the surface of activated silicone endotracheal tube to obtain a highly effective antibacterial endotracheal tube.

2. The method for preparing the highly effective antibacterial endotracheal tube according to claim 1, characterized in that: The first activator comprises: one or more of diphenylmethane diisocyanate, isophorone diisocyanate, hexamethylene diisocyanate, and naphthalene diisocyanate; And / or, the second activator includes: one or more of ethylene oxide, propylene oxide, epichlorohydrin, styrene oxide, and 1,2-butylene oxide.

3. The method for preparing the highly effective antibacterial endotracheal tube according to claim 1, characterized in that: In step S1, the first activation treatment includes: S11: placing ofloxacin in a solvent and stirring to obtain an ofloxacin solution; S12: placing the first activator in a solvent and stirring to obtain a first activator solution; S13: adding the first activator solution dropwise to the ofloxacin solution, stirring, adding water to the reaction solution, filtering, taking out the solid mixture, washing, purifying and drying, to obtain activated ofloxacin.

4. The method for preparing the highly effective antibacterial endotracheal tube according to claim 3, characterized in that: The solvents in step S11 and step 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: reaction temperature of 30-50°C, dropwise addition rate of (1-2) mL / min, and reaction time of 10-24 h after dropwise addition is completed; And / or, water is added to the reaction solution to precipitate the reactants, the solid mixture is filtered and washed with water for 1-3 times, purified by recrystallization, and dried at 50-80° C. for 24-48 hours.

5. The method for preparing the highly effective antibacterial endotracheal tube according to claim 1, characterized in that: In step S2, the second activation treatment includes: S21: placing salbutamol in a solvent and stirring to obtain a salbutamol solution; S22: placing the second activator in a solvent and stirring to obtain a second activator solution; S23: adding the second activator solution dropwise to the salbutamol solution, stirring, adding water to the reaction solution, filtering, taking out the solid mixture, washing, purifying, and drying to obtain activated salbutamol.

6. The method for preparing the highly effective antibacterial endotracheal tube according to claim 5, characterized in that: The solvents in step S21 and step S22 both include one or more of dichloromethane, tetrahydrofuran, and ethyl acetate; and / or, the molar ratio of the 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.; And / or, in step S23, the reaction conditions include: pH 8-9, reaction temperature 30-50°C, dropwise addition rate (1-2) mL / min, and reaction time after dropwise addition is 10-24 h; And / or, water is added to the reaction solution to precipitate the reactants, the solid mixture is filtered and washed with water for 1-3 times, purified by recrystallization, and dried at 50-80° C. for 24-48 hours.

7. The method for preparing a highly effective 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, air flow rate 90-110mL / min, air pressure 50-70Pa, and etching time 30-60s.

8. The method for preparing a highly effective antibacterial endotracheal tube according to claim 1, characterized in that: Step S4 specifically includes the following steps: S41: placing the activated ofloxacin obtained in step S1 in a solvent and stirring to obtain an activated ofloxacin solution; S42: placing the activated salbutamol obtained in step S2 in a solvent and stirring to obtain an activated salbutamol solution; S43: After mixing the activated ofloxacin solution and the activated salbutamol solution, the mixture is stirred to obtain a mixed solution, and then the activated silicone endotracheal cannula is immersed in the mixed solution to obtain a highly effective antibacterial endotracheal cannula.

9. The method for preparing the highly effective antibacterial endotracheal tube according to claim 8, characterized in that: The solvents in step S41 and step S42 include one or more of dimethyl sulfoxide, dichloromethane, and acetone; And / or, step S43 includes: mixing the activated ofloxacin solution and the activated salbutamol solution at 40-60°C, stirring for 4-6 hours to obtain a mixed solution, then immersing the activated silicone endotracheal cannula in the mixed solution for 5-10 minutes, slowly taking it out and placing it in a sealed container with a humidity of 80-100%, drying it at a temperature of 50-70°C for 25-35 minutes, repeating 2-4 times, taking out the silicone endotracheal cannula, placing it in a sealed container with a humidity of 80-100%, and placing it at 45-55°C for 15-24 hours to obtain a highly effective antibacterial endotracheal cannula.

10. A highly effective antibacterial endotracheal cannula prepared by the method for preparing a highly effective antibacterial endotracheal cannula as claimed in any one of claims 1 to 9.

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