A coating with lubrication, bacteriostasis and sustained-release properties, and a preparation method and application thereof

Abstract

The application discloses a coating with lubricating, bacteriostatic and sustained-release characteristics and a preparation method and application thereof, and belongs to the technical field of medical materials, wherein the preparation method of the coating comprises the following steps: [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide, a crosslinking agent and an initiator are added into a solvent and mixed to obtain a solution A; polyvinylpyrrolidone and lithium chloride are added into the solution A and stirred to obtain a solution B; zinc oxide and a surfactant are added into the solution B and ultrasonic treatment is carried out to obtain a uniform suspension; lidocaine is added into eucalyptus oil and stirred to obtain a solution C; the solution C is added into the above suspension and ultrasonic treatment is carried out to obtain a Pickering emulsion; and the Pickering emulsion is subjected to ultraviolet light irradiation treatment to obtain the coating with the lubricating, bacteriostatic and sustained-release characteristics. When the coating is applied to the surface of a urinary catheter, the friction of the urinary catheter can be reduced, the urinary catheter is endowed with excellent bacteriostatic characteristics, and excellent drug sustained-release performance can be exhibited.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, specifically to a coating with lubricating, antibacterial, and sustained-release properties, its preparation method, and its application. Background Technology

[0002] With the increasing aging of the global population and the rise in the number of people with chronic diseases, the demand for invasive urinary catheters is also growing. Common medical catheters are usually made of silicone or latex. The hydrophobic properties of these materials can lead to bacterial adhesion and biofilm formation, resulting in urinary tract infections. Meanwhile, catheter insertion is an invasive procedure that can cause adverse reactions in conscious users, such as anxiety, increased heart rate, and elevated blood pressure due to pain during insertion and removal. Indwelling catheters can cause prolonged urethral and bladder distension or discomfort, leading to emotional instability during postoperative recovery, severely impacting the user's quality of life, and even causing postoperative bleeding and other adverse reactions.

[0003] The aforementioned problems not only cause additional pain to patients, but also affect the placement of the urinary catheter, seriously impacting the treatment outcome and potentially increasing medical costs. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing a coating with lubricating, antibacterial, and slow-release properties, so as to solve the problems mentioned in the background art.

[0005] To achieve the above objectives, the embodiments of the present invention provide the following technical solutions:

[0006] A method for preparing a coating with lubricating, antibacterial, and slow-release properties includes the following steps:

[0007] [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, crosslinking agent, and initiator are added to a solvent and mixed, and stirred to obtain solution A;

[0008] Polyvinylpyrrolidone and lithium chloride were added to solution A and stirred to obtain solution B;

[0009] Zinc oxide and a surfactant were added to solution B, and the solution was subjected to ultrasonic treatment to obtain a homogeneous suspension.

[0010] Lidocaine was added to Artemisia argyi oil and stirred to obtain solution C;

[0011] Solution C was added to the above suspension and subjected to ultrasonic treatment to obtain Pickering emulsion;

[0012] Pickering emulsion was treated with ultraviolet light to obtain a coating with lubricating, antibacterial, and slow-release properties.

[0013] Preferably, the solvent is water.

[0014] Preferably, the surfactant is Tween-20.

[0015] Preferably, the mass ratio of polyvinylpyrrolidone, lithium chloride and zinc oxide is (1-3):(4-6):(0.6-1).

[0016] Preferably, the amount of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide added per milliliter of solvent is 0.05-0.15 g.

[0017] Preferably, the amount of lidocaine added per milliliter of Artemisia argyi oil is 0.5-1.5g.

[0018] Another objective of this invention is to provide a coating prepared by the above-described method.

[0019] Another objective of this invention is to provide an application of the above-described coating in the preparation of medical materials.

[0020] Another objective of this invention is to provide a medical material having the above-mentioned coating attached to its surface.

[0021] The method for preparing a coating with lubricating, antibacterial, and sustained-release properties provided in this invention involves preparing a Pickering emulsion through layer-by-layer encapsulation of lidocaine, Artemisia argyi oil, and zinc oxide / surfactant, which is used for antibacterial and sustained-release purposes. Additionally, a double-network hydrogel coating is prepared using [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide and polyvinylpyrrolidone via salting-out effect for lubrication. By integrating these two components, a hydrogel-based coating is prepared, thereby endowing the coating with lubricating, antibacterial, and drug-controlled-release properties. When applied to the surface of a urinary catheter, this coating reduces catheter friction, imparts excellent antibacterial properties, and exhibits excellent drug-controlled-release performance. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the surface lubrication performance of the coating before and after wetting, provided in Embodiment 1 of the present invention;

[0023] Figure 2 The results of frictional force and friction coefficient between the coating and the catheter provided in Embodiment 1 and Comparative Examples 1-3 of the present invention are shown in the figure.

[0024] Figure 3 This is a diagram showing the biocompatibility results of the coating provided in Example 1 of the present invention;

[0025] Figure 4 This is a schematic diagram illustrating the sustained-release performance of the coating provided in Example 1 of the present invention in PBS buffer.

[0026] Figure 5 This is a diagram illustrating the antibacterial effect of the coating provided in Embodiment 1 of the present invention;

[0027] Figure 6 The images show a comparison of a urinary catheter without the coating and a urinary catheter with the coating provided in Embodiment 1 of the present invention.

[0028] Figure 7 This is a schematic diagram of the coating mechanical property test experiment provided in Embodiment 1 of the present invention. Detailed Implementation

[0029] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0030] This invention provides a coating with antibacterial, lubricating, and controlled-release properties based on a drug-loaded Pickering emulsion encapsulated in a dual-network hydrogel. The preparation process is simple, convenient, and inexpensive, and it can be applied to the surface of insertable urinary catheters.

[0031] Specifically, in one embodiment of the present invention, a method for preparing a coating with lubricating, antibacterial, and slow-release properties is provided, comprising the following steps:

[0032] S1. [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, crosslinking agent, and initiator are added to a solvent and mixed, and stirred to obtain solution A;

[0033] S2. Add polyvinylpyrrolidone and lithium chloride to solution A and stir to obtain solution B;

[0034] S3. Add zinc oxide and surfactant to solution B and sonicate to obtain a homogeneous suspension.

[0035] S4. Add lidocaine to Artemisia argyi oil and stir to obtain solution C;

[0036] S5. Add solution C to the above suspension and sonicate to obtain Pickering emulsion;

[0037] S6. The Pickering emulsion is subjected to ultraviolet light irradiation to obtain a coating with lubricating, antibacterial and slow-release properties.

[0038] In a preferred embodiment of the present invention, the solvent is water, but is not limited thereto.

[0039] In a preferred embodiment of the present invention, the surfactant is Tween-20, but is not limited thereto; in addition, the crosslinking agent can be polyethylene glycol diacrylate (PEGDA), and the initiator can be the commercially available 1173 photoinitiator, but is not limited thereto.

[0040] In a preferred embodiment of the present invention, the mass ratio of polyvinylpyrrolidone, lithium chloride and zinc oxide is (1-3):(4-6):(0.6-1).

[0041] In a preferred embodiment of the present invention, the amount of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide added per milliliter of solvent is 0.05-0.15 g.

[0042] In a preferred embodiment of the present invention, the amount of lidocaine added per milliliter of Artemisia argyi oil is 0.5-1.5g.

[0043] In another embodiment of the present invention, the application of the above-described coating in the preparation of medical materials is also provided. Specifically, the medical material has the above-described coating attached to its surface. It should be noted that the medical materials include, but are not limited to, urinary catheters.

[0044] In this embodiment of the invention, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide and polyvinylpyrrolidone are selected, which can combine with free water through electrostatic interaction and hydrogen bonding, respectively, thereby synergistically forming a hydration layer. This synergistically formed hydration layer provides better hydration and lubrication than a single component, resulting in a lower coefficient of friction. Furthermore, this embodiment of the invention utilizes the salting-out effect to reduce the polymer solubility, generating chain entanglement and improving the mechanical properties of the coating.

[0045] In this embodiment of the invention, the mugwort oil used is a plant essential oil, whose bactericidal properties can work synergistically with the anti-adhesion properties of the lubricating layer to inhibit bacteria, thereby achieving a better antibacterial effect.

[0046] Furthermore, this invention utilizes Artemisia argyi oil to load lidocaine, which significantly enhances the solubility of lidocaine (a hydrophobic drug) within the system. Simultaneously, the presence of a concentration difference between the oil and water allows for a uniform and sustained release of the drug. More importantly, the maximum solubility of the drug in water ensures a minimum effective drug concentration while limiting the maximum amount released, preventing side effects from excessive drug concentration.

[0047] The following embodiments are some specific implementation examples and application examples of the present invention in practical applications, but are not limited thereto.

[0048] Example 1: This example provides a method for preparing a coating with lubricating, antibacterial, and slow-release properties, which includes the following steps:

[0049] S1. Add 0.5g of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide (SMBA), 0.5g of crosslinking agent PEGDA, and 10μL of 1173 photoinitiator to 5mL of water and mix, and stir to obtain a clear solution A.

[0050] S2. Add 2g of polyvinylpyrrolidone and 5g of lithium chloride to the above solution A, and stir at room temperature to obtain solution B;

[0051] S3. Add 0.8 g of zinc oxide and 186 μL of Tween-20 to the above solution B, and sonicate to obtain a homogeneous suspension.

[0052] S4. Add 5g of lidocaine to 5mL of Artemisia argyi oil and stir to obtain a homogeneous and transparent solution C.

[0053] S5. Take 1.5 mL of the above solution C and add it to the above suspension, and sonicate to obtain a stable Pickering emulsion.

[0054] S6. The above Pickering emulsion is subjected to ultraviolet light irradiation to obtain a coating with antibacterial, lubricating and controlled-release properties.

[0055] Example 2: This example provides a method for preparing a coating with lubricating, antibacterial, and slow-release properties, which includes the following steps:

[0056] S1. Add 0.25g of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide, 0.5g of crosslinking agent PEGDA, and 10μL of 1173 photoinitiator to 5mL of water and mix, and stir to obtain a clear solution A.

[0057] S2. Add 1g of polyvinylpyrrolidone and 4g of lithium chloride to the above solution A, and stir at room temperature to obtain solution B;

[0058] S3. Add 0.6 g of zinc oxide and 186 μL of Tween-20 to the above solution B, and sonicate to obtain a homogeneous suspension.

[0059] S4. Add 2.5g of lidocaine to 5mL of Artemisia argyi oil and stir to obtain a homogeneous and transparent solution C.

[0060] S5. Take 1.5 mL of the above solution C and add it to the above suspension, and sonicate to obtain a stable Pickering emulsion.

[0061] S6. The above Pickering emulsion is subjected to ultraviolet light irradiation to obtain a coating with antibacterial, lubricating and controlled-release properties.

[0062] Example 3: This example provides a method for preparing a coating with lubricating, antibacterial, and slow-release properties, which includes the following steps:

[0063] S1. Add 0.75g of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide, 0.5g of crosslinking agent PEGDA, and 10μL of 1173 photoinitiator to 5mL of water and mix, and stir to obtain a clear solution A.

[0064] S2. Add 3g of polyvinylpyrrolidone and 6g of lithium chloride to the above solution A, and stir at room temperature to obtain solution B;

[0065] S3. Add 1g of zinc oxide and 186μL of Tween-20 to the above solution B, and sonicate to obtain a homogeneous suspension.

[0066] S4. Add 7.5g of lidocaine to 5mL of Artemisia argyi oil and stir to obtain a homogeneous and transparent solution C.

[0067] S5. Take 1.5 mL of the above solution C and add it to the above suspension, and sonicate to obtain a stable Pickering emulsion.

[0068] S6. The above Pickering emulsion is subjected to ultraviolet light irradiation to obtain a coating with antibacterial, lubricating and controlled-release properties.

[0069] Example 4: This example provides a method for preparing a coating with lubricating, antibacterial, and slow-release properties, which includes the following steps:

[0070] S1. Add 0.4 g of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide, 0.5 g of crosslinking agent PEGDA, and 10 μL of 1173 photoinitiator to 5 mL of water and mix, and stir to obtain a clear solution A;

[0071] S2. Add 1.5g of polyvinylpyrrolidone and 4.5g of lithium chloride to the above solution A, and stir at room temperature to obtain solution B;

[0072] S3. Add 0.7g of zinc oxide and 186μL of Tween-20 to the above solution B, and sonicate to obtain a homogeneous suspension.

[0073] S4. Add 4g of lidocaine to 5mL of Artemisia argyi oil and stir to obtain a homogeneous and transparent solution C.

[0074] S5. Take 1.5 mL of the above solution C and add it to the above suspension, and sonicate to obtain a stable Pickering emulsion.

[0075] S6. The above Pickering emulsion is subjected to ultraviolet light irradiation to obtain a coating with antibacterial, lubricating and controlled-release properties.

[0076] Example 5: This example provides a method for preparing a coating with lubricating, antibacterial, and slow-release properties, which includes the following steps:

[0077] S1. Add 0.6 g of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide, 0.5 g of crosslinking agent PEGDA, and 10 μL of 1173 photoinitiator to 5 mL of water and mix, and stir to obtain a clear solution A;

[0078] S2. Add 2.5g of polyvinylpyrrolidone and 5.5g of lithium chloride to the above solution A, and stir at room temperature to obtain solution B;

[0079] S3. Add 0.8 g of zinc oxide and 186 μL of Tween-20 to the above solution B, and sonicate to obtain a homogeneous suspension.

[0080] S4. Add 6g of lidocaine to 5mL of Artemisia argyi oil and stir to obtain a homogeneous and transparent solution C.

[0081] S5. Take 1.5 mL of the above solution C and add it to the above suspension, and sonicate to obtain a stable Pickering emulsion.

[0082] S6. The above Pickering emulsion is subjected to ultraviolet light irradiation to obtain a coating with antibacterial, lubricating and controlled-release properties.

[0083] Comparative Example 1: This comparative example provides a method for preparing a coating, which includes the following steps:

[0084] S1. Add 0.5g of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide, 0.5g of crosslinking agent PEGDA, and 10μL of 1173 photoinitiator to 5mL of water and mix, and stir to obtain a clear solution A.

[0085] S2. The above solution A is subjected to ultraviolet light irradiation to obtain a coating.

[0086] Comparative Example 2: This comparative example provides a method for preparing a coating, which includes the following steps:

[0087] S1. Add 0.5g of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide, 0.5g of crosslinking agent PEGDA, and 10μL of 1173 photoinitiator to 5mL of water and mix, and stir to obtain a clear solution A.

[0088] S2. Add 2g of polyvinylpyrrolidone and 5g of zinc chloride to the above solution A, and stir at room temperature to obtain solution B;

[0089] S3. The above solution B is subjected to ultraviolet light irradiation to obtain a coating.

[0090] Comparative Example 3: This comparative example provides a method for preparing a coating, which includes the following steps:

[0091] S1. Add 0.5g of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonylpropyl)ammonium hydroxide, 0.5g of crosslinking agent PEGDA, and 10μL of 1173 photoinitiator to 5mL of water and mix, and stir to obtain a clear solution A.

[0092] S2. Add 2g of polyvinylpyrrolidone and 5g of lithium chloride to the above solution A, and stir at room temperature to obtain solution B;

[0093] S3. The above solution B is subjected to ultraviolet light irradiation to obtain a coating.

[0094] Experimental Example: 1. Place the weights on the surface of a glass substrate with the coating provided in Example 1, and fix the substrate at a certain angle to the table. Then, add a few drops of water to the surface of the glass substrate and observe the change in the position of the weights. The experimental results are as follows: Figure 1 As shown; wherein, when the glass substrate coated with the above coating is dry, a weight of about 5N can adhere to it, and after the surface is wetted with water, the weight slides naturally along the inclined surface, indicating that the coating prepared in the embodiment of the present invention has good lubrication performance in a liquid environment.

[0095] II. The lubrication performance of the catheter coating (the coating provided in Example 1) was tested using a friction tester. Two samples from each of the experimental and control groups were immersed in PBS solution for 30 seconds, and then placed on a V-groove plate using a clamp. A standard slider of a certain mass was gently placed on the sample, and moved along the arrow direction at a speed of 100 mm / min via the sensor linkage. The friction force and coefficient of friction were then measured. Finally, the average value of the six samples was taken as the friction force and coefficient of friction. The friction force and coefficient of friction of the coatings provided in Example 1 and Comparative Examples 1-3 were tested for 400 seconds using the above method, and the results are as follows: Figure 2 As shown; Figure 2In the figures, SMBA+LiCl+emulsion refers to the coating of Example 1, SMBA refers to the coating of Comparative Example 1, SMBA+LiCl refers to the coating of Comparative Example 2, and SMBA+ZnCl2 refers to the coating of Comparative Example 3. The figure shows that the average coefficient of friction of the coating provided in Example 1 is 0.052, and the frictional force is 0.013 N. Meanwhile, the embodiments of the present invention conducted 180 cycles of reciprocating testing on catheters coated with the above-mentioned coatings to ensure the frictional stability of the coating. The results show that the coefficient of friction of the coated catheter remains around 0.05, and the frictional force remains around 0.015 N, indicating that the coating obtained in the embodiments of the present invention has good frictional stability.

[0096] 3. 3T3-NIH cells were seeded at a density of 5000 cells per well into 96-well plates and cultured for 12 hours. The culture medium was replaced with different concentrations of PAM / IC extract (100 μL), and cultured for 24 hours. Cell viability was measured using a CCK-8 assay kit. The absorbance of the solution was detected at 450 nm using a Multiskan FC microplate reader (Thermo, USA). Cell viability (%) was defined as Abst / Absc × 100%, where Abst and Absc represent the absorbance values ​​of the test sample and control sample, respectively. The biocompatibility of the coating provided in Example 1 was tested according to the above method, and the results are as follows: Figure 3 As shown, when the coating extract concentration reached 10 mg / mL, the cell survival rate remained at 88.6% after 48 hours of culture, indicating that the PPT blend had good biocompatibility. Meanwhile, when the coating extract concentration was less than or equal to 7.5 mg / mL, the cell survival rate was greater than 100%, indicating that the cells exhibited good viability and proliferation capacity.

[0097] IV. Take 8g of the coating prepared according to the method provided in Example 1 and place it in a beaker containing 500mL of PBS solution. Place the beaker in a constant temperature shaker at 37°C and a shaking rate of 86rpm / min. Take samples at regular intervals and measure the absorbance using a UV-Vis spectrophotometer. Perform an in vitro release experiment on the coating provided in Example 1 according to the above method. The results are as follows... Figure 4 As shown, the coating can stably release lidocaine in PBS buffer for up to 150 hours, with a cumulative release rate of up to 87%, which meets the requirements for the duration of anesthesia for indwelling urinary catheters in most clinical applications.

[0098] 5. Resuscitate the bacteria onto Columbia blood agar plates, remove colonies, and resuspend in PBS to prepare 10... 4CFU / mL bacterial suspension. Take 100 μL and spread it evenly onto Columbia blood agar plates. Place the antibacterial material on the surface of the culture medium inoculated with bacteria and incubate upside down at 37°C for 12 hours. After removal, observe the bacterial growth in the petri dish. Measure and record the diameter of the inhibition zone (i.e., the area around the material where no sterile growth occurs). The antibacterial effect of the coating provided in Example 1 was tested according to the above method, and the results are as follows: Figure 5 As shown in the figure, the coating has a distinct antibacterial ring, indicating that the coating prepared in this embodiment of the invention has significant antibacterial properties.

[0099] VI. Place the urinary catheter in the Pickering emulsion prepared in Example 1 for 30 seconds, remove the catheter, and irradiate it with a 365nm wavelength ultraviolet lamp for 10 minutes. This will form a coating with antibacterial, lubricating, and controlled-release properties on the surface of the catheter. Observe the changes on the coated surface, such as... Figure 6 As shown; Figure 6 The left image shows a catheter without the coating, and the right image shows a catheter with the coating. As can be seen from the images, there is no significant change in the surface of the catheter before and after coating application, indicating that the coating provided in this embodiment of the invention can be well applied to the surface of the catheter.

[0100] 7. Take 8g of the Pickering emulsion prepared according to the method provided in Example 1 and place it in a petri dish (90mm in diameter). Irradiate with a 365nm wavelength ultraviolet lamp for 10 minutes. After the coating has cured, fix one end of the coating and pull it at a uniform speed to test the mechanical properties of the coating. The results are as follows. Figure 7 As shown in the figure, the coating can be stretched to approximately 1 meter, indicating that the coating provided in this embodiment of the invention has excellent mechanical properties and can adhere to the surface of the catheter without breaking when pulled along with the catheter.

[0101] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification.

Claims

1. A method for producing a coating having lubricating, bacteriostatic, and sustained-release properties, characterized by, The method comprises the following steps: [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide, a crosslinking agent and an initiator are mixed in a solvent to obtain solution A; polyvinylpyrrolidone and lithium chloride are added to solution A to obtain solution B; zinc oxide and a surfactant are added to solution B and ultrasonic treatment is performed to obtain a uniform suspension; lidocaine is added to the oil of Artemisia argyi to obtain solution C; solution C is added to the suspension and ultrasonic treatment is performed to obtain a Pickering emulsion; the Pickering emulsion is treated by ultraviolet irradiation to obtain a coating with lubricating, bacteriostatic and sustained-release properties.

2. The method for preparing the coating with lubricating, antibacterial, and slow-release properties according to claim 1, characterized in that, The solvent is water.

3. The method for preparing the coating with lubricating, antibacterial, and slow-release properties according to claim 1, characterized in that, The surfactant is Tween-20.

4. The method for preparing the coating with lubricating, antibacterial, and slow-release properties according to claim 1, characterized in that, The mass ratio of polyvinylpyrrolidone, lithium chloride and zinc oxide is (1-3):(4-6):(0.6-1).

5. The method for preparing a coating with lubricating, antibacterial, and slow-release properties according to claim 1 or 2, characterized in that, The amount of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide added in each milliliter of the solvent is 0.05-0.15 g.

6. The method for preparing the coating with lubricating, antibacterial, and slow-release properties according to claim 1, characterized in that, The amount of lidocaine added in each milliliter of the oil of Artemisia argyi is 0.5-1.5 g.

7. A coating prepared by the method of any one of claims 1-6.

8. Use of the coating of claim 7 in the preparation of a medical material.

9. A medical material, characterized by The surface of the medical material is attached with the coating of claim 7.

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