Slow-release dressing for local surface long-acting anesthesia and preparation method thereof

Abstract

The invention discloses a slow-release dressing for local surface long-acting anesthesia and a preparation method of the slow-release dressing, and belongs to the technical field of anesthesia dressings. The preparation method of the slow-release dressing for local surface long-acting anesthesia is used for solving the technical problems that in the prior art, the slow-release rate of an anesthesia dressing cannot be adjusted according to the tolerance of a patient to anesthetics, and the duration time of the anesthesia dressing needs to be further prolonged. Comprising the following steps: uniformly coating skin-friendly base cloth with anesthesia sustained-release gel to form an anesthesia sustained-release layer on the skin-friendly base cloth; coating the top of the anesthesia sustained-release layer with composite gel to form a water-absorbing and moisturizing layer; laying an antibacterial non-woven fabric on the top of the water-absorbing and moisture-preserving layer to obtain a primary anesthetic dressing product. The anesthesia sustained-release gel and the composite gel are matched with each other, so that the duration time of the anesthesia dressing is effectively prolonged, the release rate of the anesthetic in the anesthesia dressing can be adjusted according to the tolerance of a patient to the anesthetic, and the anesthesia effect of the anesthesia dressing is improved.

Description

Technical Field

[0001] The invention relates to the technical field of anesthesia dressings, and in particular to a sustained-release dressing for local surface long-acting anesthesia and a preparation method thereof. Background Art

[0002] In the medical field, local surface anesthesia is a common and important treatment method. In the preparation of sustained-release anesthetic dressings, the selection and ratio of anesthetic drugs are crucial. Commonly used anesthetic drugs include lidocaine, bupivacaine, etc. These drugs have the characteristics of good anesthetic effect and high safety. However, different anesthetic drugs differ in release rate, duration of action, etc., so it is necessary to make a reasonable ratio according to actual needs to achieve the best anesthetic effect.

[0003] In the prior art, a Chinese invention patent with publication number CN112791070A discloses an anesthetic dressing and a preparation method thereof. The anesthetic dressing includes an anesthetic layer and a heating layer, the anesthetic layer is a gel containing anesthetic drugs and anesthetic drug sustained-release microspheres, and the heating layer includes an isolation membrane adjacent to the anesthetic layer, a self-heating material, and a breathable membrane in sequence. The anesthetic dressing provided by the present invention is simple and convenient to use, easy to apply, and does not need to be cleaned after use; the anesthetic dressing uses anesthetic drugs and anesthetic drug sustained-release microcapsules to extend the duration of the anesthetic effect, and uses heating to shorten the onset time of the anesthetic drug, so that the anesthetic dressing has the advantages of fast onset of anesthetic effect and long duration, and can be widely used in various surgeries requiring surface anesthesia, and is also convenient for postoperative analgesia and the treatment of various intractable pains.

[0004] However, existing anesthetic dressings usually only have a stable release rate when used. In clinical practice, different people have different tolerance to anesthetics. Traditional anesthetic dressings cannot adjust the release rate of anesthetic drugs in anesthetic dressings according to the patient's tolerance to anesthetics, and the anesthesia duration of existing anesthetic dressings needs to be further improved.

[0005] In view of the technical defects in this aspect, a solution is now proposed. Summary of the invention

[0006] The purpose of the present invention is to provide a sustained-release dressing for local surface long-acting anesthesia and a preparation method thereof, so as to solve the technical problems in the prior art that the sustained-release rate of anesthesia dressings cannot be adjusted according to the patient's tolerance to anesthetics and the duration of anesthesia dressings needs to be further improved.

[0007] The purpose of the present invention can be achieved through the following technical solutions:

[0008] The preparation method of a sustained-release dressing for local surface long-acting anesthesia comprises the following steps:

[0009] S1. Evenly coating the anesthetic sustained-release gel on the skin-friendly base fabric to form an anesthetic sustained-release layer on the skin-friendly base fabric;

[0010] S2, coating the composite gel on the top of the anesthetic sustained-release layer to form a water-absorbing and moisturizing layer;

[0011] S3, laying antibacterial non-woven fabric on the top of the water absorption and moisture retention layer to obtain a primary anesthesia dressing;

[0012] S4. Use a heat sealer to heat seal the edge of the initial anesthesia dressing to obtain the anesthesia dressing.

[0013] Furthermore, in step S1, the skin-friendly base fabric is a hydrophilic and lipophilic amphiphilic non-woven fabric, and the coating amount of the anesthetic sustained-release gel is 0.8-1g / cm2; in step S2, the coating amount of the composite gel is 3-5g / cm2.

[0014] Furthermore, the preparation method of the anesthetic sustained-release gel is as follows: hydroxymethyl cellulose and deionized water are added to a three-necked flask and stirred until the system is dissolved, anesthesia-loaded microspheres are added to the three-necked flask, ultrasonically dispersed for 50-70 minutes, and post-processed to obtain the anesthetic sustained-release gel.

[0015] Furthermore, the dosage ratio of the hydroxymethyl cellulose, deionized water and anesthetic-loaded microspheres is 1g:100mL:3g, and the post-treatment includes: after the reaction is completed, standing for 24 hours, absorbing the upper clear liquid, and transferring the bottom precipitate to a freeze dryer at a temperature of -30°C for freeze drying to obtain an anesthetic sustained-release gel.

[0016] Further, the anesthetic-loaded microspheres are processed by the following steps:

[0017] A1, adding lidocaine free base, polylactic acid-co-glycolic acid and dichloromethane into a three-necked flask and stirring until the system is dissolved to obtain a mixed solution;

[0018] A2. Slowly add the mixed solution into a high-speed shear emulsifier containing polyvinyl alcohol solution. After homogenization and emulsification, the emulsion is pressed through a microporous membrane at a uniform speed, and then post-processed to obtain anesthetic-loaded microspheres.

[0019] The synthetic reaction principle of anesthesia-loaded microspheres is:

[0020] By using dichloromethane as a solvent, polylactic acid-glycolic acid copolymer and lidocaine free base are promoted to mix evenly to form a uniform mixed solution. Polyvinyl alcohol is used as an emulsifier to reduce the surface tension of the solution and promote the formation of microspheres. The size of the microspheres is controlled by a microporous membrane to obtain anesthetic-loaded microspheres with relatively uniform size.

[0021] Furthermore, in step A1, the amount ratio of lidocaine free base, polylactic acid-glycolic acid copolymer and dichloromethane is 1g:10g:50ml; in step A2, the volume ratio of the mixed solution to the polyvinyl alcohol solution is 1:10, the polyvinyl alcohol solution is composed of polyvinyl alcohol and deionized water in an amount ratio of 1g:100mL, the rotation speed of the high-speed shear emulsifier is 3000-3500rpm, the pore size of the microporous membrane is 3-10μm, and the post-treatment includes: distilling off dichloromethane at room temperature, sedimentation aging for 30-50min, centrifugation, washing the filter cake with deionized water 3 times and then drying it, and transferring the filter cake to a freeze dryer at a temperature of -30°C for freeze drying to obtain anesthetic-loaded microspheres.

[0022] Furthermore, the preparation method of lidocaine free base is: add lidocaine hydrochloride and deionized water into a three-necked flask, stir at room temperature, add ammonia water dropwise into the three-necked flask, adjust the system pH to 11-12, stir for 20-30 minutes, and post-treat to obtain lidocaine free base.

[0023] The synthetic reaction principle of lidocaine free base is:

[0024] Lidocaine hydrochloride forms a uniform solution in deionized water, and the pH of the reaction system is adjusted by ammonia water. Hydroxyl ions in the ammonia water react with hydrogen ions in the lidocaine hydrochloride molecules to generate water, thereby releasing lidocaine free base, which is then freeze-dried to obtain lidocaine free base.

[0025] Furthermore, the composite gel is obtained by processing the following steps:

[0026] B1. Add bentonite and activation solution into a three-necked flask and stir. Raise the temperature of the three-necked flask to 70-80° C., keep warm and stir for 40-50 min, and post-treat to obtain activated bentonite.

[0027] B2. Add activated bentonite, hydroxymethyl cellulose and N,N,-dimethylformamide into a three-necked flask protected by nitrogen and ultrasonically disperse for 30-50 minutes. Stir the three-necked flask, raise the temperature of the three-necked flask to 70-80°C, stir until the system is dissolved, drop triphenylmethane triisocyanate into the three-necked flask, keep warm and stir for 2-3 hours, and post-treat to obtain a composite gel.

[0028] The synthetic reaction principle of composite gel is:

[0029] The bentonite is activated by an activation liquid to improve its surface activity. Triphenylmethane triisocyanate is used as a cross-linking agent. Triphenylmethane triisocyanate can react with hydroxymethyl cellulose and hydroxyl groups in the activated bentonite, thereby connecting the bentonite particles with the polymer chains to form a composite gel network structure, thereby preparing a composite gel.

[0030] Furthermore, in step B1, the amount ratio of the bentonite and the activation solution is 1g:7-8mL, the activation solution is composed of 5-8mol / L nitric acid and 20wt% hydrogen peroxide in a volume ratio of 5:2, and the post-treatment includes: after the reaction is completed, the temperature of the three-necked flask is lowered to room temperature, suction filtration is performed, the filter cake is washed with purified water until neutral and then dried, the filter cake is transferred to a drying oven at a temperature of 70-80°C, and vacuum dried to constant weight to obtain activated bentonite; in step B2, the amount ratio of the activated bentonite, hydroxymethyl cellulose, N,N,-dimethylformamide and triphenylmethane triisocyanate is 1g:2g:20mL:0.5-0.6g, and the post-treatment includes: after the reaction is completed, suction filtration is performed, the filter cake is washed with purified water 3 times and then dried, and the filter cake is transferred to a freeze dryer at a temperature of -30°C for freeze drying to obtain a composite gel.

[0031] A sustained-release dressing for local surface long-acting anesthesia is prepared by a preparation method of a sustained-release dressing for local surface long-acting anesthesia.

[0032] The present invention has the following beneficial effects:

[0033] 1. The sustained-release dressing for local surface long-term anesthesia of the present invention uses lidocaine free base as an active ingredient for anesthesia, mixes it with polylactic acid-glycolic acid copolymer, forms hydrogen bonds between amino groups in the molecule of lidocaine free base and carboxyl groups or ester groups in the molecule of polylactic acid-glycolic acid copolymer, and coats microspheres with polylactic acid-glycolic acid copolymer in the form of a load, and enhances the stability of the microspheres, prevents the drug from agglomerating or precipitating during the preparation or storage process, and after hydroxymethyl cellulose is dissolved in water, its molecular chains can be interwoven to form a three-dimensional network structure, and the interweaving of hydroxymethyl cellulose molecular chains and the filling of anesthetic-loaded microspheres form a filling and supporting effect, when the gel contacts the body surface, the gel gradually swells and releases the anesthetic drug through the penetration of water molecules, and the network structure of hydroxymethyl cellulose and the regulating effect of water molecules jointly prolong the release time of the anesthetic drug, so that the release rate of the drug can be more accurately controlled, and the diffusion rate of the anesthetic drug in the gel is limited, thereby meeting the demand for long-term sustained release on the body surface.

[0034] 2. The sustained-release dressing for local surface long-term anesthesia of the present invention activates bentonite to improve its surface activity and makes the activated bentonite more easily dispersed in the hydroxymethyl cellulose solution. The cross-linked network system constructed by the activated bentonite and hydroxymethyl cellulose makes the network structure of the gel more compact and stable, which helps to limit the movement and diffusion of water molecules in the gel and improve the hygroscopicity and water retention of the mixed gel. When the anesthetic dressing contacts the skin, the composite gel in the water-absorbing and moisturizing layer easily absorbs external moisture and increases its own moisture content. The skin-friendly base fabric layer has good amphiphilic properties and forms an oily skin layer. The cross-linked interface between the material and the aqueous material allows the anesthetic component to be released to the skin surface to achieve the anesthetic effect; the anesthetic sustained-release layer and the water-absorbing and moisturizing layer both contain hydroxymethyl cellulose. As the temperature rises, the interaction between the hydroxymethyl cellulose molecular chains weakens, causing the gel network structure to become relatively loose, and the temperature increase will accelerate the movement of water molecules, thereby accelerating the swelling process of the gel, allowing the anesthetic to be released to the body surface faster, thereby shortening the release time. By controlling the temperature of the dressing, refrigerated storage can be achieved, and the sustained-release rate of the anesthetic can be controlled by controlling the temperature of the dressing during use to meet the anesthesia needs of patients with different anesthesia tolerance. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] 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.

[0036] Figure 1 It is a schematic diagram of the structure of the anesthesia dressing in the present invention.

[0037] In the figure: 100, skin-friendly base fabric; 200, anesthetic sustained-release layer; 300, water-absorbing and moisturizing layer; 400, antibacterial non-woven fabric. DETAILED DESCRIPTION

[0038] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0039] In the present application, the poly(lactic acid-co-glycolic acid) is composed of 55% lactic acid and 45% glycolic acid.

[0040] Example 1

[0041] This embodiment provides a method for preparing an anesthetic sustained-release gel for a sustained-release dressing for local surface long-term anesthesia, comprising the following steps:

[0042] A1. Preparation of Lidocaine Free Base

[0043] Add lidocaine hydrochloride and deionized water in a ratio of 1 g: 2 mL into a three-necked flask, stir at room temperature, add 25 wt % ammonia water dropwise into the three-necked flask, adjust the system pH to 11, stir for 20 min, filter, wash the filter cake with purified water 3 times and then dry it, transfer the filter cake to a freeze dryer at -30 ° C and freeze-dry to obtain lidocaine free base.

[0044] A2. Preparation of anesthetic-loaded microspheres

[0045] Add lidocaine free base, polylactic acid-co-glycolic acid and dichloromethane in a ratio of 1 g:10 g:50 mL into a three-necked flask and stir until the system is dissolved to obtain a mixed solution;

[0046] Add polyvinyl alcohol and deionized water at a ratio of 1g:100mL into a three-necked flask and stir until the system is dissolved. Then add it into a high-speed shear emulsifier, set the speed of the high-speed shear emulsifier to 3000rpm, and slowly add the mixed solution into the high-speed shear emulsifier at a volume ratio of the mixed solution to the polyvinyl alcohol solution of 1:10. Homogenize and emulsify for 30 minutes, press it through a microporous membrane with a pore size of 3μm at a uniform speed, evaporate dichloromethane at room temperature, and age it by sedimentation for 30 minutes. Centrifuge, wash the filter cake three times with deionized water and then drain it. Transfer the filter cake to a freeze dryer at -30°C for freeze drying to obtain anesthetic-loaded microspheres.

[0047] A3. Preparation of anesthetic sustained-release gel

[0048] Weigh: 20 g of hydroxymethyl cellulose and 2000 mL of deionized water, add into a three-necked flask and stir until the system is dissolved, add 60 g of anesthetic-loaded microspheres into the three-necked flask, ultrasonically disperse for 50 min, let stand for 24 h, absorb the upper clear liquid, transfer the bottom precipitate to a freeze dryer at -30 °C and freeze-dry to obtain an anesthetic sustained-release gel.

[0049] Example 2

[0050] This embodiment provides a method for preparing an anesthetic sustained-release gel for a sustained-release dressing for local surface long-term anesthesia, comprising the following steps:

[0051] A1. Preparation of Lidocaine Free Base

[0052] Add lidocaine hydrochloride and deionized water in a ratio of 1 g: 2 mL into a three-necked flask, stir at room temperature, add 25 wt % ammonia water dropwise into the three-necked flask, adjust the system pH to 11.5, stir for 25 min, filter, wash the filter cake with purified water 3 times and then drain, transfer the filter cake to a freeze dryer at -30°C and freeze-dry, and obtain lidocaine free base with a water content of 35 wt %.

[0053] A2. Preparation of anesthetic-loaded microspheres

[0054] Add lidocaine free base, polylactic acid-co-glycolic acid and dichloromethane in a ratio of 1 g:10 g:50 mL into a three-necked flask and stir until the system is dissolved to obtain a mixed solution;

[0055] Add polyvinyl alcohol and deionized water at a ratio of 1g:100mL into a three-necked flask and stir until the system is dissolved. Then add it into a high-speed shear emulsifier. Set the speed of the high-speed shear emulsifier to 3300rpm. Slowly add the mixed solution into the high-speed shear emulsifier at a volume ratio of 1:10 between the mixed solution and the polyvinyl alcohol solution. Homogenize and emulsify for 40 minutes. Press it through a microporous membrane with a pore size of 7μm at a uniform speed. Dichloromethane is evaporated at room temperature. The mixture is aged by sedimentation for 40 minutes. Centrifuge, wash the filter cake three times with deionized water and then dry it. Transfer the filter cake to a freeze dryer at -30°C for freeze drying to obtain anesthetic-loaded microspheres.

[0056] A3. Preparation of anesthetic sustained-release gel

[0057] Weigh: 20g of hydroxymethyl cellulose and 2000mL of deionized water are added into a three-necked flask and stirred until the system is dissolved. 60g of anesthetic-loaded microspheres are added into the three-necked flask, ultrasonically dispersed for 60min, allowed to stand for 24h, and after absorbing the upper clear liquid, the bottom precipitate is transferred to a freeze dryer at -30°C and freeze-dried to obtain an anesthetic sustained-release gel with a water content of 40wt%.

[0058] Example 3

[0059] This embodiment provides a method for preparing an anesthetic sustained-release gel for a sustained-release dressing for local surface long-term anesthesia, comprising the following steps:

[0060] A1. Preparation of Lidocaine Free Base

[0061] Add lidocaine hydrochloride and deionized water in a ratio of 1 g: 2 mL into a three-necked flask, stir at room temperature, add 25 wt % ammonia water dropwise into the three-necked flask, adjust the system pH to 12, stir for 20-30 min, filter, wash the filter cake with purified water 3 times and then drain, transfer the filter cake to a freeze dryer at -30 ° C and freeze-dry to obtain lidocaine free base.

[0062] A2. Preparation of anesthetic-loaded microspheres

[0063] Add lidocaine free base, polylactic acid-co-glycolic acid and dichloromethane in a ratio of 1 g:10 g:50 mL into a three-necked flask and stir until the system is dissolved to obtain a mixed solution;

[0064] Add polyvinyl alcohol and deionized water at a ratio of 1g:100mL into a three-necked flask and stir until the system is dissolved. Then add it into a high-speed shear emulsifier. Set the speed of the high-speed shear emulsifier to 3500rpm. Slowly add the mixed solution into the high-speed shear emulsifier at a volume ratio of 1:10 between the mixed solution and the polyvinyl alcohol solution. Homogenize and emulsify for 50 minutes. Press it through a microporous membrane with a pore size of 10μm at a uniform speed. Evaporate dichloromethane at room temperature. Aged for 50 minutes after sedimentation. Centrifuge. Wash the filter cake three times with deionized water and then drain it. Transfer the filter cake to a freeze dryer at -30°C for freeze drying to obtain anesthetic-loaded microspheres.

[0065] A3. Preparation of anesthetic sustained-release gel

[0066] Weigh: 20 g of hydroxymethyl cellulose and 2000 mL of deionized water, add into a three-necked flask and stir until the system is dissolved, add 60 g of anesthetic-loaded microspheres into the three-necked flask, ultrasonically disperse for 70 min, let stand for 24 h, absorb the upper clear liquid, transfer the bottom precipitate to a freeze dryer at -30 ° C and freeze-dry to obtain an anesthetic sustained-release gel with a water content of 45 wt%.

[0067] Example 4

[0068] This embodiment provides a method for preparing a composite gel for a sustained-release dressing for local surface long-term anesthesia, comprising the following steps:

[0069] B1. Preparation of activated bentonite

[0070] 5 mol / L nitric acid and 20 wt % hydrogen peroxide were mixed uniformly in a volume ratio of 5:2 to obtain an activation solution;

[0071] Bentonite and activation solution were added into a three-necked flask at a ratio of 1 g:7 mL and stirred. The temperature of the three-necked flask was raised to 70°C and stirred for 40 minutes. The temperature of the three-necked flask was lowered to room temperature and filtered. The filter cake was washed with purified water until it was neutral and then dried. The filter cake was transferred to a drying oven at a temperature of 70°C and vacuum dried to constant weight to obtain activated bentonite.

[0072] B2. Preparation of composite gel

[0073] Weigh: 40 g of activated bentonite, 80 g of hydroxymethyl cellulose and 800 mL of N,N,-dimethylformamide, add them into a three-necked flask protected by nitrogen, and ultrasonically disperse for 30 minutes. The three-necked flask is stirred, the temperature of the three-necked flask is increased to 70°C, and stirred until the system is dissolved. 20 g of triphenylmethane triisocyanate is added dropwise to the three-necked flask, and the mixture is stirred for 2 hours at this temperature. The filter cake is washed three times with purified water and then dried. The filter cake is transferred to a freeze dryer at a temperature of -30°C and freeze-dried to obtain a composite gel with a water content of 35 wt%.

[0074] Example 5

[0075] This embodiment provides a method for preparing a composite gel for a sustained-release dressing for local surface long-term anesthesia, comprising the following steps:

[0076] B1. Preparation of activated bentonite

[0077] 7 mol / L nitric acid and 20 wt % hydrogen peroxide were mixed uniformly in a volume ratio of 5:2 to obtain an activation solution;

[0078] Bentonite and activation solution were added into a three-necked flask at a ratio of 1 g:7.5 mL and stirred. The temperature of the three-necked flask was raised to 75°C and stirred for 45 minutes. The temperature of the three-necked flask was lowered to room temperature and filtered. The filter cake was washed with purified water until it was neutral and then dried. The filter cake was transferred to a drying oven at a temperature of 75°C and vacuum dried to constant weight to obtain activated bentonite.

[0079] B2. Preparation of composite gel

[0080] Weigh: 40 g of activated bentonite, 80 g of hydroxymethyl cellulose and 800 mL of N,N,-dimethylformamide, add them into a three-necked flask protected by nitrogen, ultrasonically disperse for 40 min, stir the three-necked flask, raise the temperature of the three-necked flask to 75°C, stir until the system is dissolved, add 22 g of triphenylmethane triisocyanate dropwise into the three-necked flask, keep stirring for 2.5 h, filter, wash the filter cake with purified water 3 times and then drain, transfer the filter cake to a freeze dryer at a temperature of -30°C and freeze-dry to obtain a composite gel with a water content of 40 wt%.

[0081] Example 6

[0082] This embodiment provides a method for preparing a composite gel for a sustained-release dressing for local surface long-term anesthesia, comprising the following steps:

[0083] B1. Preparation of activated bentonite

[0084] 8 mol / L nitric acid and 20 wt % hydrogen peroxide were mixed uniformly in a volume ratio of 5:2 to obtain an activation solution;

[0085] Bentonite and activation solution were added into a three-necked flask at a ratio of 1 g:8 mL and stirred. The temperature of the three-necked flask was raised to 80°C and stirred for 50 minutes. The temperature of the three-necked flask was lowered to room temperature and filtered. The filter cake was washed with purified water until it was neutral and then dried. The filter cake was transferred to a drying oven at a temperature of 80°C and vacuum dried to constant weight to obtain activated bentonite.

[0086] B2. Preparation of composite gel

[0087] Weigh: 40 g of activated bentonite, 80 g of hydroxymethyl cellulose and 800 mL of N,N,-dimethylformamide, add them into a three-necked flask protected by nitrogen, ultrasonically disperse for 50 min, stir the three-necked flask, raise the temperature of the three-necked flask to 80°C, stir until the system is dissolved, add 24 g of triphenylmethane triisocyanate dropwise into the three-necked flask, keep stirring for 3 h, filter, wash the filter cake with purified water 3 times and then drain, transfer the filter cake to a freeze dryer at a temperature of -30°C and freeze-dry to obtain a composite gel with a water content of 45 wt%.

[0088] Example 7

[0089] See also Figure 1 This embodiment provides a method for preparing a sustained-release dressing for local surface long-term anesthesia, comprising the following steps:

[0090] S1, select hydrophilic and lipophilic non-woven fabric as skin-friendly base fabric 1, press 0.8g / cm 2 The anesthetic sustained-release gel prepared in Example 1 is evenly coated on the skin-friendly base fabric 1 to form an anesthetic sustained-release layer 2 on the skin-friendly base fabric 1;

[0091] S2, press 3g / cm 2 The composite gel prepared in Example 4 is evenly coated on the top of the anesthetic sustained-release layer 2 to form a water-absorbing and moisturizing layer 3;

[0092] S3, laying antibacterial non-woven fabric on the top of the water absorption and moisture retention layer to obtain a primary anesthesia dressing;

[0093] S4. Use a heat sealer to heat seal the edge of the initial anesthesia dressing to obtain the anesthesia dressing.

[0094] Example 8

[0095] The difference between this embodiment and embodiment 7 is that in step S1, the anesthetic sustained-release gel is prepared by embodiment 2, and the coating amount is 0.9 g / cm 2 In step S2, the composite gel is prepared by Example 5, and the coating amount is 4g / cm 2 .

[0096] Example 9

[0097] The difference between this embodiment and embodiment 7 is that in step S1, the anesthetic sustained-release gel is prepared by embodiment 3, and the coating amount is 1 g / cm 2 In step S2, the composite gel is prepared by Example 6, and the coating amount is 5g / cm 2 .

[0098] Comparative Example 1

[0099] The difference between this comparative example and Example 7 is that, when preparing the anesthetic sustained-release gel prepared in Example 1, step A1 is omitted, and lidocaine hydrochloride in step A1 is used to replace lidocaine free base in step A2.

[0100] Comparative Example 2

[0101] The difference between this comparative example and Example 7 is that, when preparing the composite gel prepared in Example 4, step B1 is omitted, and the activated bentonite in step B2 is replaced by the bentonite in step B1.

[0102] Comparative Example 3

[0103] The difference between this comparative example and Example 7 is that, when preparing the composite gel prepared in Example 4, step B1 is omitted, and no activated bentonite is added in step B2.

[0104] Performance Test:

[0105] The anesthetic dressings prepared in Examples 7-9 and Comparative Examples 1-3 were used on different patients. The anesthetic onset time and anesthetic efficacy duration of the anesthetic dressings at different temperatures were measured in a room temperature environment with a humidity of 45-50%. Each group of data was tested on 20 patients, and the extreme values ​​were removed to express the average value. The specific test results are shown in Table 1 below.

[0106] Table 1-Performance test data of the sample

[0107]

[0108] Data Analysis:

[0109] A comparative analysis of the data in the above table shows that the sustained-release anesthetic dressing prepared by the present invention has an anesthetic onset time of 11 minutes, and the anesthetic effect lasts for a long time. Moreover, the release efficiency of the anesthetic drug of the sustained-release anesthetic dressing prepared by the present invention is directly related to the temperature. In actual use, the dressing can be temperature-controlled and heated by an external heat source to change the release efficiency of the anesthetic drug in the anesthetic dressing according to the anesthesia tolerance of different patients, so as to achieve the best anesthetic effect. Moreover, when the temperature is higher than 35°C, the release rate of the anesthetic component in the dressing will not change greatly, so as to avoid the continuous and large-scale release of a large amount of anesthetic components accompanied by the increase in temperature, thereby ensuring the safety of medication.

[0110] The above contents are merely examples and explanations of the structure of the present invention. The technicians in this technical field may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the structure of the invention or exceed the scope defined by the claims, they should all fall within the protection scope of the present invention.

[0111] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0112] The preferred embodiments of the present invention disclosed above are only used to help explain the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to only specific implementation methods. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing a sustained-release dressing for local surface long-term anesthesia, characterized in that: The following steps are involved: S1, evenly coating the anesthetic sustained-release gel on the skin-friendly base fabric (1) to form an anesthetic sustained-release layer (2) on the skin-friendly base fabric; S2, coating the composite gel on the top of the anesthetic sustained-release layer (2) to form a water-absorbing and moisturizing layer (3); S3, laying the antibacterial non-woven fabric (4) on the top of the water absorption and moisture retention layer (3) to obtain a primary anesthetic dressing; S4. Use a heat sealer to heat seal the edge of the initial anesthesia dressing to obtain the anesthesia dressing.

2. The method for preparing the sustained-release dressing for local surface long-acting anesthesia according to claim 1, characterized in that: In step S1, the skin-friendly base fabric is a hydrophilic and lipophilic non-woven fabric, and the coating amount of the anesthetic sustained-release gel is 0.8-1 g / cm 2 In step S2, the coating amount of the composite gel is 3-5g / cm 2 .

3. The method for preparing the sustained-release dressing for local surface long-acting anesthesia according to claim 1, characterized in that: The preparation method of the anesthetic sustained-release gel is as follows: hydroxymethyl cellulose and deionized water are added into a three-necked flask and stirred until the system is dissolved, anesthetic-loaded microspheres are added into the three-necked flask, ultrasonically dispersed for 50-70 minutes, and post-treated to obtain the anesthetic sustained-release gel, wherein the dosage ratio of the hydroxymethyl cellulose, deionized water and anesthetic-loaded microspheres is 1g:100mL:3g.

4. The method for preparing the sustained-release dressing for local surface long-acting anesthesia according to claim 3, characterized in that: The anesthetic-loaded microspheres were processed by the following steps: A1, adding lidocaine free base, polylactic acid-co-glycolic acid and dichloromethane into a three-necked flask and stirring until the system is dissolved to obtain a mixed solution; A2. Slowly add the mixed solution into a high-speed shear emulsifier containing polyvinyl alcohol solution. After homogenization and emulsification, the emulsion is pressed through a microporous membrane at a uniform speed, and then post-processed to obtain anesthetic-loaded microspheres.

5. The method for preparing the sustained-release dressing for local surface long-acting anesthesia according to claim 4, characterized in that: In step A1, the amount ratio of lidocaine free base, polylactic acid-glycolic acid copolymer and dichloromethane is 1g:10g:50ml; in step A2, the volume ratio of the mixed solution to the polyvinyl alcohol solution is 1:10, the polyvinyl alcohol solution is composed of polyvinyl alcohol and deionized water in a dosage ratio of 1g:100mL, the rotation speed of the high-speed shear emulsifier is 3000-3500rpm, and the pore size of the microporous membrane is 3-10μm.

6. The method for preparing the sustained-release dressing for local surface long-acting anesthesia according to claim 4, characterized in that: The preparation method of lidocaine free base is as follows: adding lidocaine hydrochloride and deionized water into a three-necked flask, stirring at room temperature, dropping ammonia water into the three-necked flask, adjusting the system pH to 11-12, stirring for 20-30 minutes, and post-treating to obtain lidocaine free base, wherein the usage ratio of lidocaine hydrochloride and deionized water is 1g:2mL.

7. The method for preparing the sustained-release dressing for local surface long-acting anesthesia according to claim 1, characterized in that: The composite gel is obtained by processing the following steps: B1. Add bentonite and activation solution into a three-necked flask and stir. Raise the temperature of the three-necked flask to 70-80° C., keep warm and stir for 40-50 min, and post-treat to obtain activated bentonite. B2. Add activated bentonite, hydroxymethyl cellulose and N,N,-dimethylformamide into a three-necked flask protected by nitrogen and ultrasonically disperse for 30-50 minutes. Stir the three-necked flask, raise the temperature of the three-necked flask to 70-80°C, stir until the system is dissolved, drop triphenylmethane triisocyanate into the three-necked flask, keep warm and stir for 2-3 hours, and post-treat to obtain a composite gel.

8. The method for preparing the sustained-release dressing for local surface long-term anesthesia according to claim 7, characterized in that: In step B1, the usage ratio of the bentonite and the activation solution is 1g:7-8mL, and the activation solution is composed of 5-8mol / L nitric acid and 20wt% hydrogen peroxide in a volume ratio of 5:2; in step B2, the usage ratio of the activated bentonite, hydroxymethyl cellulose, N,N,-dimethylformamide and triphenylmethane triisocyanate is 1g:2g:20mL:0.5-0.6g.

9. A sustained-release dressing for local surface long-term anesthesia, characterized in that: The sustained-release dressing for local surface long-acting anesthesia is prepared by the method for preparing the sustained-release dressing for local surface long-acting anesthesia according to any one of claims 1 to 8.

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