A coating with anesthetic and antibacterial functions and preparation method thereof

Abstract

The present invention belongs to the field of medical coatings, and specifically relates to a coating with anesthetic and antibacterial functions and a preparation method thereof. The preparation method comprises the following steps: (I) preparation of a base coating, (II) preparation of a drug-loaded hydrogel coating, and (III) preparation of a coating with anesthetic and antibacterial functions. The preparation method of the present invention solves the problems of insufficient drug loading, easy shedding, irritation, and uneven release of nanoparticles on the one hand, and solves the problem of unsatisfactory long-term release performance of hydrogels on the other hand. By pretreating the base material (such as a medical catheter) and integrating multiple functions (anesthetic, antibacterial), a product suitable for multiple scenarios can be prepared, which can greatly reduce adverse reactions of the body while facilitating clinical use, and reduce the risk of secondary intubation and tracheotomy.

Description

Technical Field

[0001] The invention belongs to the field of medical coatings, and in particular relates to a coating with anesthetic and antibacterial functions and a preparation method thereof. Background Art

[0002] Hydrogel is a polymer material with a three-dimensional network structure, usually composed of natural or synthetic polymers, with good biocompatibility and high water content, and is often used in biomedical fields such as drug release systems, tissue engineering and wound dressings. In recent years, with the development of nanotechnology, the combination of hydrogel and nanoparticles has gradually become a research hotspot, showing many advantages in drug delivery.

[0003] Clinical anesthesia methods are generally divided into general anesthesia, regional anesthesia, local anesthesia, and surface anesthesia. Surface anesthesia is usually performed to reduce the patient's pain and discomfort and relieve the patient's anxiety during certain superficial surgeries or examinations. Surface anesthesia is uniformly applied directly to the skin or mucosal surface to block the stimulation of superficial nerve endings.

[0004] Therefore, during clinical intubation, many problems are often encountered, such as mucosal damage, excessive stress response, inflammation, insufficient drug loading of hydrogel coating, uneven drug release, and insufficient coating strength.

[0005] Therefore, based on this, the technical solution of the present invention is proposed. Summary of the invention

[0006] Hydrogel is a polymer material with a three-dimensional network structure, usually composed of natural or synthetic polymers, with good biocompatibility and high water content, and is often used in biomedical fields such as drug release systems, tissue engineering and wound dressings. In recent years, with the development of nanotechnology, the combination of hydrogel and nanoparticles has gradually become a research hotspot, showing many advantages in drug delivery.

[0007] Clinical anesthesia methods are generally divided into general anesthesia, regional anesthesia, local anesthesia, and surface anesthesia. Surface anesthesia is usually performed to reduce the patient's pain and discomfort and relieve the patient's anxiety during certain superficial surgeries or examinations. Surface anesthesia is uniformly applied directly to the skin or mucosal surface to block the stimulation of superficial nerve endings.

[0008] Therefore, during clinical intubation, many problems are often encountered, such as mucosal damage, excessive stress response, inflammation, insufficient drug loading of hydrogel coating, uneven drug release, and insufficient coating strength.

[0009] Therefore, based on this, the technical solution of the present invention is proposed. Summary of the invention

[0011] In order to solve the problems existing in the prior art, the present invention provides a method for preparing a coating having anesthesia and antibacterial functions, the preparation method comprising the following steps:

[0012] (I) Preparation of base coating

[0013] (1) mixing sodium periodate, dopamine, polyallylamine hydrochloride and pH buffer to obtain a base solution;

[0014] (2) soaking the substrate material in the substrate solution to react, and then washing to obtain a substrate coating;

[0015] (II) Preparation of drug-loaded hydrogel coating

[0016] (3) placing the drug-loaded particles into the anesthetic drug solution and shaking them, centrifuging them after completion, and discarding the supernatant to obtain the drug-loaded particles;

[0017] (4) mixing carboxymethyl chitosan, a buffer, an anesthetic, the drug-loaded particles and a cross-linking agent in sequence to obtain a hydrogel;

[0018] (5) placing the base coating into the hydrogel for molding to obtain a drug-loaded hydrogel coating;

[0019] (III) Preparation of final coating

[0020] (6) The drug-loaded hydrogel coating is subjected to antibacterial photocuring modification to obtain the coating having anesthetic and antibacterial functions.

[0021] Preferably, in step (1), the pH of the substrate solution is 5;

[0022] And / or, the pH buffer is sodium acetate buffer with a concentration of 10-200 mg / L;

[0023] and / or, in the substrate solution, the concentration of sodium periodate is 1-5 mg / mL;

[0024] and / or, in the base solution, the concentration of dopamine is 0.5-4 mg / mL;

[0025] And / or, in the base solution, the concentration of polyallylamine hydrochloride is 0.1-2 mg / mL.

[0026] Preferably, in step (2), the base material is a medical catheter material;

[0027] And / or, the reaction temperature is 20-25°C;

[0028] And / or, the reaction time is 1 to 2 hours.

[0029] Preferably, in step (3), the drug-loaded particles are one of mesoporous silica, graphene oxide particles, Mxene particles, calcium alginate microspheres, calcium carbonate microspheres, and polylactic acid microspheres;

[0030] And / or, the anesthetic drug solution consists of an anesthetic drug and a solvent, the anesthetic drug is lidocaine hydrochloride (concentration is 50-500 mg / mL), and the solvent is water or ethanol;

[0031] And / or, the shaking time is 22 to 26 hours;

[0032] And / or, the centrifugation method is: centrifugation at 500-3000 g for 5-15 min.

[0033] It should be emphasized that if the selected drug-loaded particles are mesoporous silica, a "wrapping" treatment is required after the drug loading in step (3) is completed. Specifically, the drug-loaded particles are immersed in a mixed solution of pH = 5 (including dopamine and sodium periodate, the concentration of dopamine is 0.5~4 mg / mL, and the concentration of sodium periodate is 1~5 mg / mL) for 5~50 minutes, and then centrifuged and the supernatant is discarded to obtain the capped drug-loaded particles. The subsequent operations can use the capped drug-loaded particles.

[0034] Preferably, in step (4), the concentration of the carboxymethyl chitosan is 10-50 mg / mL;

[0035] And / or, the buffer is a citric acid buffer or a tris buffer, the pH of the buffer is 5.0-7.0, and the concentration of the buffer is 0.2-2 mol / L;

[0036] And / or, the anesthetic drug is lidocaine hydrochloride, and the concentration of the anesthetic drug is 10-300 mg / mL;

[0037] and / or, the concentration of the drug-loaded particles is 5 to 80 mg / mL;

[0038] And / or, the cross-linking agent is genipin or glutaraldehyde, and the concentration of the cross-linking agent is 0.1-2 mg / mL.

[0039] Preferably, in step (5), the molding temperature is 37-60° C., and the molding time is 1-12 hours.

[0040] Preferably, in step (6), the wavelength of the light curing is 365 nm, and the light curing irradiation time is 10 to 60 minutes.

[0041] It should be emphasized that there are two modification methods for step (6), one is a "one-step method" and the other is a "step-by-step method", specifically:

[0042] "One-step method": Apply a mixed solution containing 0.5~4mg / mL dopamine, 0.5~3mg / mL thiol hyaluronic acid, and 0.5~3mg / mL caffeic acid on the drug-loaded hydrogel coating and irradiate it under 365nm ultraviolet light for 10~60min.

[0043] "Step-by-step method": Soak the drug-loaded hydrogel coating in a mixed solution of pH = 5 (including dopamine and sodium periodate, the concentration of dopamine is 0.5~4mg / mL, and the concentration of sodium periodate is 1~5mg / mL) at 20~25℃ for 1h, then rinse the residual solution with distilled water, and finally apply a mixed solution containing 0.5~3mg / mL of thiol hyaluronic acid and 0.5~3mg / mL of caffeic acid, and irradiate under 365nm ultraviolet light for 10~60min.

[0044] Based on the same technical concept, another solution of the present invention is to provide a coating having anesthetic and antibacterial functions obtained by the above preparation method.

[0045] The beneficial effects of the present invention are:

[0046] The preparation method of the present invention solves the problems of insufficient drug loading, easy shedding, irritation, uneven release, etc. of nanoparticles on the one hand, and solves the problem of unsatisfactory long-term release performance of hydrogel drugs on the other hand.

[0047] By pre-treating the base material (such as medical catheters) and integrating multiple functions (anesthesia, antibacterial), products suitable for multiple scenarios can be prepared. While facilitating clinical use, they can greatly reduce the body's adverse reactions and reduce the risk of secondary intubation and tracheotomy. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0049] Figure 1 This is a comparison chart of lidocaine hydrochloride release within 12 hours.

[0050] Figure 2 This is a comparison chart of lidocaine hydrochloride release from 6 hours to 7 days.

[0051] Figure 3 This is the total element distribution spectrum of the Mxene drug-loaded coating surface.

[0052] Figure 4This is the total element distribution spectrum of the mesoporous silica drug-loaded coating surface.

[0053] Figure 5 This is a real picture of the culture medium inoculated with Pseudomonas aeruginosa.

[0054] Figure 6 This is a photo of a culture medium containing a sample of Pseudomonas aeruginosa.

[0055] Figure 7 This is a real picture of the culture medium inoculated with surface Staphylococcus.

[0056] Figure 8 This is a real picture of the culture medium of Staphylococcus aureus with the sample placed on the surface.

[0057] Fig. 9 This is a real picture of the culture medium inoculated with substances within the inhibition zone for cultivation.

[0058] Fig.10 This is a real picture of the culture medium inoculated with substances outside the inhibition zone for cultivation. DETAILED DESCRIPTION

[0059] To make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described in detail below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other implementation methods obtained by ordinary technicians in this field without creative work belong to the scope of protection of the present invention.

[0060] Example 1

[0061] This embodiment provides a method for preparing a coating having anesthesia and antibacterial functions, the preparation method comprising the following steps:

[0062] (I) Preparation of base coating

[0063] (1) mixing sodium periodate, dopamine, polyallylamine hydrochloride and pH buffer to obtain a base solution; wherein the concentration of sodium periodate is 1 mg / mL, the concentration of dopamine is 0.5 mg / mL, and the concentration of polyallylamine hydrochloride is 0.1 mg / mL;

[0064] (2) Immersing the medical catheter in the substrate solution at 20° C. for 2 hours to react, and after completion, washing the residual liquid with distilled water to obtain a medical catheter containing a substrate coating;

[0065] (II) Preparation of drug-loaded hydrogel coating

[0066] (3) The drug-loaded Mxene particles are placed in an anesthetic solution (including lidocaine hydrochloride and water, with a lidocaine hydrochloride concentration of 50 mg / mL) and shaken for 22 hours. After completion, centrifuge and discard the supernatant to obtain drug-loaded particles;

[0067] (4) Under stirring conditions, carboxymethyl chitosan, citric acid buffer (containing citric acid and sodium citrate), lidocaine hydrochloride, the drug-loaded particles and genipin are mixed in sequence to obtain a hydrogel; wherein the concentration of carboxymethyl chitosan is 10 mg / mL, the concentration of citric acid is 100 mg / mL, the concentration of sodium citrate is 50 mg / mL, the concentration of lidocaine hydrochloride is 10 mg / mL, the concentration of the drug-loaded particles is 5 mg / mL, and the concentration of genipin is 0.1 mg / mL;

[0068] (5) placing the medical catheter comprising the base coating into a mold, injecting the hydrogel, and then placing the mold in an oven at 37° C. for molding for 12 hours to obtain a medical catheter comprising a drug-loaded hydrogel coating;

[0069] (III) Preparation of final coating

[0070] (6) A mixed solution containing 0.5 mg / mL dopamine, 0.5 mg / mL thiohyaluronic acid, and 0.5 mg / mL caffeic acid is applied to a medical catheter containing a drug-loaded hydrogel coating, and the mixture is irradiated under 365 nm ultraviolet light for 10 min to obtain the coating having anesthetic and antibacterial functions.

[0071] Example 2

[0072] This embodiment provides a method for preparing a coating having anesthesia and antibacterial functions, the preparation method comprising the following steps:

[0073] (I) Preparation of base coating

[0074] (1) mixing sodium periodate, dopamine, polyallylamine hydrochloride and pH buffer to obtain a base solution; wherein the concentration of sodium periodate is 1 mg / mL, the concentration of dopamine is 0.5 mg / mL, and the concentration of polyallylamine hydrochloride is 0.1 mg / mL;

[0075] (2) Immersing the medical catheter in the substrate solution at 20° C. for 2 hours to react, and after completion, washing the residual liquid with distilled water to obtain a medical catheter containing a substrate coating;

[0076] (II) Preparation of drug-loaded hydrogel coating

[0077] (3) The mesoporous silica to be loaded with drugs is placed in an anesthetic drug solution (including lidocaine hydrochloride and water, with a lidocaine hydrochloride concentration of 50 mg / mL) and shaken for 22 hours. After completion, the mixture is centrifuged and the supernatant is discarded to obtain drug-loaded particles. The drug-loaded particles are further immersed in a mixed solution of pH = 5 (including dopamine and sodium periodate, with a dopamine concentration of 0.5 mg / mL and a sodium periodate concentration of 1 mg / mL) for capping for 50 minutes, and then centrifuged and the supernatant is discarded to obtain capped drug-loaded particles.

[0078] (4) Under stirring conditions, carboxymethyl chitosan, citric acid buffer (containing citric acid and sodium citrate), lidocaine hydrochloride, the blocked drug-loaded particles and genipin are mixed in sequence to obtain a hydrogel; wherein the concentration of carboxymethyl chitosan is 10 mg / mL, the concentration of citric acid is 50 mg / mL, the concentration of sodium citrate is 100 mg / mL, the concentration of lidocaine hydrochloride is 10 mg / mL, the concentration of blocked drug-loaded particles is 5 mg / mL, and the concentration of genipin is 0.1 mg / mL;

[0079] (5) placing the medical catheter comprising the base coating into a mold, injecting the hydrogel, and then placing the mold in an oven at 37° C. for molding for 12 hours to obtain a medical catheter comprising a drug-loaded hydrogel coating;

[0080] (III) Preparation of final coating

[0081] (6) A mixed solution containing 0.5 mg / mL dopamine, 0.5 mg / mL thiohyaluronic acid, and 0.5 mg / mL caffeic acid is applied to a medical catheter containing a drug-loaded hydrogel coating, and the mixture is irradiated under 365 nm ultraviolet light for 10 min to obtain the coating having anesthetic and antibacterial functions.

[0082] Example 3

[0083] This embodiment provides a method for preparing a coating having anesthesia and antibacterial functions, the preparation method comprising the following steps:

[0084] (I) Preparation of base coating

[0085] (1) mixing sodium periodate, dopamine, polyallylamine hydrochloride and pH buffer to obtain a base solution; wherein the concentration of sodium periodate is 5 mg / mL, the concentration of dopamine is 4 mg / mL, and the concentration of polyallylamine hydrochloride is 2 mg / mL;

[0086] (2) Immersing the medical catheter in the substrate solution at 25° C. for 1 hour for reaction, and then washing the residual liquid with distilled water to obtain a medical catheter containing a substrate coating;

[0087] (II) Preparation of drug-loaded hydrogel coating

[0088] (3) The drug-loaded Mxene particles are placed in an anesthetic solution (including lidocaine hydrochloride and ethanol, with a lidocaine hydrochloride concentration of 500 mg / mL) and shaken for 26 hours. After completion, centrifuge and discard the supernatant to obtain drug-loaded particles;

[0089] (4) Under stirring conditions, carboxymethyl chitosan, tris buffer (containing tris(hydroxymethylaminomethane) and hydrochloric acid), lidocaine hydrochloride, the drug-loaded particles and glutaraldehyde are mixed in sequence to obtain a hydrogel; wherein the concentration of carboxymethyl chitosan is 50 mg / mL, the concentration of tris(hydroxymethylaminomethane) is 50 mg / mL, the amount of dilute hydrochloric acid (10%) is 5 mL, the concentration of lidocaine hydrochloride is 300 mg / mL, the concentration of the drug-loaded particles is 80 mg / mL, and the concentration of glutaraldehyde is 2 mg / mL;

[0090] (5) placing the medical catheter comprising the base coating into a mold, injecting the hydrogel, and then placing the mold in an oven at 60° C. for molding for 1 hour to obtain a medical catheter comprising a drug-loaded hydrogel coating;

[0091] (III) Preparation of final coating

[0092] (6) The medical catheter containing the drug-loaded hydrogel coating is immersed in a mixed solution of pH = 5 (including dopamine and sodium periodate, the concentration of dopamine is 4 mg / mL, and the concentration of sodium periodate is 5 mg / mL) at 25°C for 1 hour, and then the residual solution is rinsed with distilled water. Finally, a mixed solution containing 3 mg / mL of thiol hyaluronic acid and 3 mg / mL of caffeic acid is applied, and irradiated under 365nm ultraviolet light for 60 minutes to obtain the coating with anesthetic and antibacterial functions.

[0093] Example 4

[0094] This embodiment provides a method for preparing a coating having anesthesia and antibacterial functions, the preparation method comprising the following steps:

[0095] (I) Preparation of base coating

[0096] (1) mixing sodium periodate, dopamine, polyallylamine hydrochloride and pH buffer to obtain a base solution; wherein the concentration of sodium periodate is 1 mg / mL, the concentration of dopamine is 0.5 mg / mL, and the concentration of polyallylamine hydrochloride is 0.1 mg / mL;

[0097] (2) Immersing the medical catheter in the substrate solution at 20° C. for 2 hours to react, and after completion, washing the residual liquid with distilled water to obtain a medical catheter containing a substrate coating;

[0098] (II) Preparation of drug-loaded hydrogel coating

[0099] (3) The mesoporous silica to be loaded with drugs is placed in an anesthetic drug solution (including lidocaine hydrochloride and water, with a lidocaine hydrochloride concentration of 50 mg / mL) and shaken for 22 hours. After completion, the mixture is centrifuged and the supernatant is discarded to obtain drug-loaded particles. The drug-loaded particles are further immersed in a mixed solution of pH = 5 (including dopamine and sodium periodate, with a dopamine concentration of 0.5 mg / mL and a sodium periodate concentration of 1 mg / mL) for capping for 50 minutes, and then centrifuged and the supernatant is discarded to obtain capped drug-loaded particles.

[0100] (4) Under stirring conditions, carboxymethyl chitosan, citric acid buffer (containing citric acid and sodium citrate), lidocaine hydrochloride, the blocked drug-loaded particles and genipin are mixed in sequence to obtain a hydrogel; wherein the concentration of carboxymethyl chitosan is 10 mg / mL, the concentration of citric acid is 20 mg / mL, the concentration of sodium citrate is 100 mg / mL, the concentration of lidocaine hydrochloride is 10 mg / mL, the concentration of blocked drug-loaded particles is 5 mg / mL, and the concentration of genipin is 0.1 mg / mL;

[0101] (5) placing the medical catheter comprising the base coating into a mold, injecting the hydrogel, and then placing the mold in an oven at 37° C. for molding for 12 hours to obtain a medical catheter comprising a drug-loaded hydrogel coating;

[0102] (III) Preparation of final coating

[0103] (6) The medical catheter containing the drug-loaded hydrogel coating is immersed in a mixed solution of pH = 5 (including dopamine and sodium periodate, the concentration of dopamine is 4 mg / mL, and the concentration of sodium periodate is 5 mg / mL) at 25°C for 1 hour, and then the residual solution is rinsed with distilled water. Finally, a mixed solution containing 3 mg / mL of thiol hyaluronic acid and 3 mg / mL of caffeic acid is applied, and irradiated under 365nm ultraviolet light for 60 minutes to obtain the coating with anesthetic and antibacterial functions.

[0104] Test example

[0105] 1. Lidocaine hydrochloride drug release test

[0106] Grouping: Mxene group, obtained by referring to the preparation method described in Example 1; mesoporous silica group, obtained by referring to the preparation method described in Example 2. The drug release percentage data of the two groups are shown in Table 1.

[0107] Table 1

[0108] time Drug release percentage in the Mxene group within 7 days / % <![CDATA[Average drug release rate in μg / h within the Mxene test interval (4 cm 2 ).]]> Drug release percentage of mesoporous silica group within 7 days / % <![CDATA[Average drug release rate within the mesoporous silica test interval, μg / h (4 cm 2 ).]]> 5min 44.23 87331.20 17.74 44498.88 15min 54.02 87331.2 32.79 18882.36 30min 64.78 9664.80 41.33 7137.84 1h 72.19 7081.20 57.43 6729.72 3h 82.98 2437.60 66.75 974.67 6h 88.27 887.88 76.33 667.72 12h 91.65 289.71 88.12 410.82 24h 95.90 92.69 95.24 123.94 3d 98.62 58.30 99.61 19.05 7d 100.00 9.32 100.00 0.84

[0109] From Table 1 and Figure 1 , Figure 2It can be seen that the Mxene group and the mesoporous silica group released 50% of the anesthetic in 15 minutes and 60 minutes respectively to complete the initial burst release of the anesthetic. Both were able to continuously release lidocaine hydrochloride during the 7-day test period, achieving the effect of sustained drug release. The amount of drug released is determined by the amount of drug added, and the amount of drug released will change with increasing or decreasing the amount of drug. Therefore, in practice, different feed ratios can be designed to produce coatings based on different anesthesia needs to adapt to various application scenarios.

[0110] (II) EDS analysis

[0111] Figure 3 The distribution of elements on the surface of the Mxene drug-loaded coating prepared in reference to Example 1 is shown in Table 2.

[0112] Table 2

[0113] time Drug release percentage in the Mxene group within 7 days / % <![CDATA[Average drug release rate within the Mxene test interval, μg / h (4 cm 2 ).]]> Drug release percentage of mesoporous silica group within 7 days / % <![CDATA[Average drug release rate within the mesoporous silica test interval, μg / h (4 cm 2 ).]]> 5min 44.23 87331.20 17.74 44498.88 15min 54.02 87331.2 32.79 18882.36 30min 64.78 9664.80 41.33 7137.84 1h 72.19 7081.20 57.43 6729.72 3h 82.98 2437.60 66.75 974.67 6h 88.27 887.88 76.33 667.72 12h 91.65 289.71 88.12 410.82 24h 95.90 92.69 95.24 123.94 3d 98.62 58.30 99.61 19.05 7d 100.00 9.32 100.00 0.84

[0114] It is necessary to explain in addition that Figure 3 Cracks can be seen in the figure. In fact, there are no cracks in the coating itself. However, since this type of hydrogel is not resistant to the strong voltage of EDS high-magnification detection, cracks will appear during the test. The coating itself will not be exposed to this voltage in its own usage scenario.

[0115] The Cl content mainly comes from lidocaine hydrochloride, N mainly comes from carboxymethyl chitosan and dopamine, S mainly comes from mercapto hyaluronic acid, Ti comes from Mxene, Al may come from the preparation process of Mxene manufacturers, and Na may come from the buffer solution.

[0116] Figure 4 The distribution of elements on the surface of the mesoporous silica drug-loaded coating prepared in reference to Example 2 is shown in Table 3.

[0117] Table 3

[0118] element Line Type wt% wt%Sigma At% C K-line system 44.74 0.49 53.17 N K-line system 3.11 0.70 3.17 O K-line system 44.95 0.47 40.10 Na K-line system 1.43 0.06 0.89 Si K-line system 3.27 0.06 1.66 S K-line system 0.11 0.03 0.05 Cl K-line system 2.39 0.06 0.96 Total 100.00 100.00

[0119] The Cl content mainly comes from lidocaine hydrochloride, N mainly comes from carboxymethyl chitosan and dopamine, S mainly comes from mercapto hyaluronic acid, Si comes from mesoporous silica, and Na may come from the buffer solution.

[0120] (III) Antibacterial analysis

[0121] The product obtained in Example 1 was used as a sample and placed in a culture medium inoculated with Pseudomonas aeruginosa (as a representative of Gram-negative bacteria) and Staphylococcus aureus (as a representative of Gram-positive bacteria). Figure 5 The culture medium inoculated with Pseudomonas aeruginosa (as blank control group) Figure 6The culture medium of Pseudomonas aeruginosa into which the sample was placed (as the experimental group). Figure 7 For the culture medium inoculated with surface Staphylococcus aureus (as blank control group), Figure 8 The sample was placed on the culture medium of Staphylococcus aureus (as the experimental group).

[0122] Depend on Figure 5~Figure 8 It can be seen that the coating samples have obvious antibacterial ability against both Gram-negative and Gram-positive bacteria, and no bacteria will grow around the material. It is particularly noteworthy that Pseudomonas aeruginosa is a pathogenic and drug-resistant bacterium, and its growth can still be significantly inhibited by the drugs released by the coating.

[0123] Furthermore, the inner and outer materials of the inhibition zone containing Pseudomonas aeruginosa were inoculated on the culture medium for culture. The results of culturing the materials in the inhibition zone showed that there were basically no bacteria in the inhibition zone (such as Fig. 9 ), while Agrobacterium aeruginosa is clearly present outside the inhibition zone (this morphology is consistent with the characteristics of Pseudomonas aeruginosa, such as Fig.10 as shown).

[0124] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art can easily think of changes or substitutions within the technical scope disclosed by the present invention, which should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A method for preparing a coating having anesthesia and antibacterial functions, characterized in that: The preparation method comprises the following steps: (I) Preparation of base coating (1) mixing sodium periodate, dopamine, polyallylamine hydrochloride and pH buffer to obtain a base solution; (2) soaking the substrate material in the substrate solution to react, and then washing to obtain a substrate coating; (II) Preparation of drug-loaded hydrogel coating (3) placing the drug-loaded particles into the anesthetic drug solution and shaking them, centrifuging them after completion, and discarding the supernatant to obtain the drug-loaded particles; (4) mixing carboxymethyl chitosan, a buffer, an anesthetic, the drug-loaded particles and a cross-linking agent in sequence to obtain a hydrogel; (5) placing the base coating into the hydrogel for molding to obtain a drug-loaded hydrogel coating; (III) Preparation of final coating (6) The drug-loaded hydrogel coating is subjected to antibacterial photocuring modification to obtain the coating having anesthetic and antibacterial functions; wherein: The antibacterial light curing modification is a one-step method or a step-by-step method; The one-step method comprises: applying a mixed solution containing dopamine, mercapto hyaluronic acid and caffeic acid on the drug-loaded hydrogel coating, and performing light curing; The step-by-step method comprises: soaking the drug-loaded hydrogel coating in a mixed solution containing dopamine and sodium periodate, washing the residual solution with distilled water, and finally applying a mixed solution containing mercapto hyaluronic acid and caffeic acid, and performing light curing.

2. The method for preparing the coating having anesthesia and antibacterial functions according to claim 1, characterized in that: In step (1), the pH of the substrate solution is 5; And / or, the pH buffer is sodium acetate buffer with a concentration of 10-200 mg / L; and / or, in the substrate solution, the concentration of sodium periodate is 1-5 mg / mL; and / or, in the base solution, the concentration of dopamine is 0.5-4 mg / mL; And / or, in the base solution, the concentration of polyallylamine hydrochloride is 0.1-2 mg / mL.

3. The method for preparing the coating having anesthesia and antibacterial functions according to claim 1, characterized in that: In step (2), the base material is a medical catheter material; And / or, the reaction temperature is 20-25°C; And / or, the reaction time is 1 to 2 hours.

4. The method for preparing the coating having anesthesia and antibacterial functions according to claim 1, characterized in that: In step (3), the drug-loaded particles are one of mesoporous silica, graphene oxide particles, Mxene particles, calcium alginate microspheres, calcium carbonate microspheres, and polylactic acid microspheres; And / or, the anesthetic drug solution consists of an anesthetic drug and a solvent, the anesthetic drug is lidocaine hydrochloride, and the solvent is water or ethanol; And / or, the shaking time is 22 to 26 hours; And / or, the centrifugation method is: centrifugation at 500-3000 g for 5-15 min.

5. The method for preparing the coating having anesthesia and antibacterial functions according to claim 1, characterized in that: In step (4), the concentration of the carboxymethyl chitosan is 10-50 mg / mL; And / or, the buffer is a citric acid buffer or a tris buffer, the pH of the buffer is 5.0-7.0, and the concentration of the buffer is 0.2-2 mol / L; And / or, the anesthetic drug is lidocaine hydrochloride, and the concentration of the anesthetic drug is 10-300 mg / mL; and / or, the concentration of the drug-loaded particles is 5 to 80 mg / mL; And / or, the cross-linking agent is genipin or glutaraldehyde, and the concentration of the cross-linking agent is 0.1-2 mg / mL.

6. The method for preparing the coating with anesthetic and antibacterial functions according to claim 1, characterized in that: In step (5), the molding temperature is 37-60° C., and the molding time is 1-12 hours.

7. The method for preparing the coating having anesthesia and antibacterial functions according to claim 1, characterized in that: In step (6), the wavelength of the light curing is 365 nm, and the light curing irradiation time is 10 to 60 minutes.

8. A coating having anesthetic and antibacterial functions obtained by the preparation method according to any one of claims 1 to 7.

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