SOD-containing patch for gouty arthritis

Abstract

The application discloses a SOD-containing patch for gouty arthritis and belongs to the fields of biological medicine and medical devices. The SOD-containing patch for gouty arthritis is prepared by compounding SOD, chondroitin sulfate A sodium salt and chitosan, can reduce the uric acid level to a higher degree, and has a good anti-inflammatory effect and swelling elimination effect. The SOD is wrapped by the chitosan-chondroitin sulfate A sodium salt compound, so that the SOD maintains the enzyme activity in the application process, the utilization rate is effectively improved, the prepared patch has high mechanical strength, the fixing ability of the patch to the joint skin can be maintained in daily activities, and the falling phenomenon does not occur.

Description

Technical Field

[0001] This invention relates to an SOD-containing patch for gouty arthritis, belonging to the fields of biomedicine and medical devices. Background Technology

[0002] Gouty arthritis is a chronic inflammatory disease caused by the precipitation of urate crystals in the synovium or other sites, leading to joint inflammation and severe joint pain and chronic structural damage, in addition to elevated blood uric acid levels. Globally, the number of people suffering from gouty arthritis is increasing year by year. Currently, commonly used uric acid-lowering drugs are mainly chemical drugs with relatively simple mechanisms of action. They have significant adverse reactions such as liver and kidney damage, and gastrointestinal toxicity, and are prone to rebound effects after discontinuation, seriously affecting the quality of life of gouty arthritis patients. Therefore, developing safe and effective products for treating gouty arthritis from natural plants and microorganisms is of great significance.

[0003] Medical research has found that patent CN103446577 B provides a pharmaceutical composition and application for the prevention and treatment of arthritis. The active ingredient, chondroitin sulfate, has the ability to reduce pain in osteoarthritis patients, improve joint function, and reduce joint swelling and effusion. In its 2003 recommendations for the treatment of osteoarthritis published by the European Federation for Rheumatology, it was considered an effective drug for treating knee osteoarthritis. The amount of chondroitin sulfate in the human body gradually decreases around the age of 20; therefore, with age, ingesting a certain dose of chondroitin sulfate can achieve a certain therapeutic effect on gouty arthritis. However, the effect of using chondroitin sulfate alone is still insufficient, especially for patients with severe inflammation, where the effects are not obvious. Superoxide dismutase (SOD) can directly convert free radicals in the body into water and oxygen, acting as the body's first line of defense against free radicals. Many studies have shown that the pathogenesis of gouty arthritis is closely related to the accumulation of endogenous ROS and causes a decrease in mitochondrial SOD expression. Increasing SOD expression can produce better anti-inflammatory and uric acid-lowering effects. Currently, there are very few reports on exogenous SOD treatment for gouty arthritis. Furthermore, the use of chondroitin sulfate and SOD to prevent and treat gouty arthritis presents challenges, including poor therapeutic effects when SOD is taken orally. Analysis suggests this is because orally taken SOD is easily inactivated in the intestines, is decomposed, and has a low effective absorption rate.

[0004] With the development of polymer microneedle technology, polymer microneedle drug delivery combines the advantages of subcutaneous injection and transdermal patch delivery, making it the most widely researched and promising type of microneedle product. Soluble microneedles, with their diverse shapes and delivery characteristics, possess irreplaceable advantages over other transdermal methods, and have enormous application and market potential in the pharmaceutical and other fields. However, current microneedle treatments for gouty arthritis still face challenges, including the inability to maintain the microneedles at the joint site for extended periods, and their tendency to slip and detach from the skin. Furthermore, SOD, as an enzyme, is prone to inactivation during the microneedle preparation process. Summary of the Invention

[0005] [Technical Issues]

[0006] The technical problem that this invention aims to solve is that microneedles cannot be fixed to joints for a long time and are prone to slipping and falling off the skin. In addition, SOD, as an enzyme, is easily deactivated during the preparation of microneedles.

[0007] [Technical Solution]

[0008] This invention prepares an SOD-containing patch for gouty arthritis. The base material used is chitosan and sodium chondroitin sulfate A. When combined with SOD, it can not only effectively relieve gouty arthritis, but also achieve long-term fixation of the patch on joints such as elbows and knees.

[0009] This invention provides an SOD-containing patch for gouty arthritis. The patch has a polymer microneedle structure, comprising a base layer and a needle tip layer. The needle tip layer includes microneedles (needle tips) arranged in an array on the base layer, and the microneedles are loaded with SOD. The substrate of the microneedles is a polymeric composite composed of chondroitin A sodium salt and chitosan.

[0010] The microneedle is conical, with a base diameter of 200 μm, a height of 800 μm, and a tip diameter of 5-10 μm.

[0011] The substrate of the microneedles is composed of chitosan and sodium chondroitin sulfate A in a mass ratio of 1:1 to 10:1, preferably 4:1. The chitosan includes chitosan with a degree of deacetylation ≥95% and a viscosity of 100-200 mPa·s.

[0012] The amount of SOD loaded in the microneedles can be 10-100000 IU / g, preferably 1000-50000 IU / g.

[0013] The base layer material is one of PE film, PVC film, PET film, EVA film, PU film, PSA film, PVA film, and PVA / PVP composite film.

[0014] This invention provides a method for preparing an SOD-containing patch for gouty arthritis, comprising the following steps:

[0015] (1) Add chitosan to an aqueous acetic acid solution, stir and mix at room temperature, dialyze for 6-8 hours to make the pH of the solution 5.2-5.4, and concentrate the chitosan solution to a concentration of 1.5-15%.

[0016] (2) After mixing the Tween-type emulsifier with the polyglycerol emulsifier, add it to the above chitosan solution and stir evenly to obtain dispersion system A;

[0017] (3) Add chondroitin sulfate A sodium salt to sterile water and stir to disperse evenly to obtain dispersion system B;

[0018] (4) At a stirring speed of 1000-2000 rpm, slowly add dispersion system B to dispersion system A, and stir at room temperature for 2-3 hours to obtain dispersion system C;

[0019] (5) Weigh SOD, dissolve it in sterile water, add it to dispersion system C, and continue stirring to obtain needle tip dispersion D;

[0020] (6) Pour the above dispersion D into the microneedle mold, distribute it evenly, and make the thickness 0.05-0.15 mm;

[0021] (7) Place the mold in a dry environment at 30-50℃ for 4-6 hours;

[0022] (8) Remove the mold and place it at room temperature. Add dispersion D again and centrifuge.

[0023] (9) Repeat steps (7) and (8) 1-5 times; remove the mold, cover the base layer, and finally peel off to obtain an SOD-containing patch for gouty arthritis.

[0024] In one embodiment of the present invention, in step (1), the concentration of the acetic acid aqueous solution can be 1% (w / v), and the ratio of chitosan to the acetic acid aqueous solution can be 2% (w / v).

[0025] In one embodiment of the present invention, in step (1), the concentration method may be rotary evaporation under reduced pressure.

[0026] In one embodiment of the present invention, in step (2), the Tween-type emulsifier is specifically one or more of Tween 80, Tween 60, and Tween 40; the polyglycerol-type emulsifier is one or more of decaglycerol monostearate, decaglycerol monooleate, decaglycerol monolaurate, hexaglycerol monooleate, and hexaglycerol monostearate. The mass ratio of the Tween-type emulsifier to the polyglycerol emulsifier can be 4:1.

[0027] In one embodiment of the present invention, in step (2), the ratio of chitosan solution to emulsifier can be 2g:15mg.

[0028] In one embodiment of the present invention, in step (3), the ratio of chondroitin A sodium salt to sterile water can be 1.5% (w / v).

[0029] In one embodiment of the present invention, in step (4), the final proportion of chondroitin A sodium salt in dispersion system C is 1.5% (w / v).

[0030] In one embodiment of the present invention, in step (5), the ratio of SOD to dispersion system C can be 1g:1mL.

[0031] [Beneficial Effects]

[0032] This invention uses a specific dosage of SOD, chondroitin A sodium salt, and chitosan in combination. Through dosage optimization and component adjustment, it can achieve excellent anti-inflammatory and swelling-reducing effects while significantly lowering uric acid levels. Furthermore, the raw materials of chondroitin A sodium salt, SOD, and chitosan are very safe, with a low likelihood of adverse reactions, showing promising application prospects in the treatment and prevention of gouty arthritis.

[0033] Compared with other drug delivery formulations, encapsulating SOD in a chitosan-chondroitin sulfate sodium salt polymeric complex allows SOD to maintain stable enzyme activity during preparation and storage, thereby ensuring therapeutic efficacy.

[0034] The patch utilizes a chitosan-chondroitin sulfate sodium salt polymer complex to prepare microneedles. When inserted into the skin near the joint, the polymer can adhere to the skin through a small amount of tissue fluid, oil, or sweat, preventing the patch from falling off and improving patient compliance. Attached Figure Description

[0035] Figure 1 This is a schematic diagram of the structure of the SOD patch in the embodiments of this application.

[0036] Figure 2 The therapeutic effect of SOD-containing patches on a rat model of hyperuricemia.

[0037] Figure 3 The therapeutic effect of SOD-containing patches on a rat model of ankle arthritis. Detailed Implementation

[0038] Example 1: A method for preparing and optimizing an SOD-containing patch for gouty arthritis.

[0039] One example of this embodiment of a SOD-containing patch for gouty arthritis is a soluble microneedle patch. For example... Figure 1 As shown, the soluble microneedle patch includes a base layer 1 and a tip layer 2 loaded with SOD. The tip layer 2 is composed of soluble microneedles arranged in an array on the base layer. The tip layer 2 contains SOD 21. The substrate 22 of the tip layer 2 is a chondroitin sulfate A sodium salt-chitosan polymer complex, which serves as both the substrate for microneedle formation and an important active ingredient. The base layer 1 is made of PVA film. The SOD patch contains 100 microneedles arranged in a 10×10 array. Each microneedle is 800 μm high, with a tip diameter of 5-10 μm and a base diameter of 200 μm. The distance between the tips is 800 μm. The SOD patch is circular, with an area of ​​1.5 cm². 2 When in use, the needle tip layer 2 absorbs water and salt from the interstitial fluid, swells to form a hydrogel, and the drugs (SOD, chondroitin A sodium salt, chitosan) are slowly released. At the same time, the active carbonyl groups in the hydrogel easily condense with the amino groups on the skin surface to form a Schiff base structure, forming a novel hydrogel network, thereby making the polymer adhere more firmly to the skin.

[0040] Specifically, in this embodiment, chitosan (degree of deacetylation ≥95%, viscosity 100-200 mPa·s) and chondroitin A sodium salt were both sourced from Shanghai Aladdin Biochemical Technology Co., Ltd. SOD was sourced from Shenzhen Zhongke Xinyang Biotechnology Co., Ltd., with a specific activity of 50,000 IU / g.

[0041] Specifically, the preparation method of the SOD-containing patch for gouty arthritis in this embodiment includes the following steps:

[0042] (1) Add 2g of chitosan to 100mL of 1% acetic acid aqueous solution, stir and mix at room temperature, dialyze for 6-8h to make the pH of the solution 5.2-5.4, and concentrate the concentration of chitosan solution to 1.5-15% by rotary evaporation under reduced pressure.

[0043] (2) After heating and mixing 12 mg Tween-80 and 3 mg decaglycerol monooleate, add them to the above chitosan solution and stir evenly to obtain dispersion system A;

[0044] (3) Weigh a certain amount of chondroitin A sodium salt, add it to 5 mL of sterile water, stir and disperse evenly to obtain dispersion system B;

[0045] (4) At a certain stirring speed, slowly add dispersion system B to dispersion system A, and stir at room temperature for 2-3 hours to obtain dispersion system C;

[0046] (5) Weigh 1g of SOD, dissolve it in 1mL of sterile water, add it to 1mL of dispersion system C, and continue stirring for 1h to obtain needle tip dispersion D;

[0047] (6) Pour the above dispersion D into the microneedle mold, distribute it evenly, and make the thickness 0.05-0.15 mm;

[0048] (7) Place the mold in a dry environment at 30-50℃ for 4-6 hours;

[0049] (8) Remove the mold and place it at room temperature. Add dispersion D again and centrifuge at 2000g for 20min.

[0050] (9) Repeat steps (7) and (8) 1-5 times, remove the above mold, cover the base layer, and finally peel off to obtain an SOD-containing patch for gouty arthritis.

[0051] In this embodiment, since the volume of the drug-containing microneedles in each patch is approximately 20 μL and the SOD enzyme activity is 25000 IU / ml, the drug loading of the patch should be 500 IU.

[0052] In this embodiment, the mass ratio of chitosan to chondroitin A sodium salt, the stirring speed in step (4), and the number of repetitions in step (7) were compared and optimized using three parameters: mechanical strength, skin fixation ability, and SOD enzyme activity. During the experiment, five patches were selected from each comparative example for testing. The specific evaluation method is as follows:

[0053] (1) Mechanical strength: Frozen mouse skin was immersed in physiological saline to restore to room temperature, and the surface moisture was wiped off. In a ventilated area, the prepared patch was vertically inserted into the mouse skin and kept for 1 hour. The patch was then removed from the mouse skin, and the treated skin was soaked in 10% formalin, embedded in paraffin, and sectioned longitudinally along the skin with a section thickness of 20 μm. The tissue cross-section was observed under an optical microscope, and the insertion depth was measured. In principle, the deeper the patch penetrates the skin, the higher the mechanical strength.

[0054] (2) Skin fixation ability: Frozen mouse skin was immersed in physiological saline to restore room temperature, and the surface moisture was wiped off to keep the skin moist and fix the skin tissue. In a ventilated area, the prepared patch was vertically inserted into the mouse skin, with the patch suspended downwards, and the time required for the patch to fall off was observed. The mouse skin needed to be kept moist throughout the experiment to evaluate its fixation ability on the skin. In principle, the longer the time required for the patch to fall off, the stronger its adhesion and fixation ability on the mouse skin.

[0055] (3) SOD enzyme activity: Dissolve the prepared patch in 1 mL of distilled water to obtain the test sample. Detect the SOD enzyme activity using the NBT method. Repeat the test three times for each sample and take the average value.

[0056] The specific enzyme activity assay method is as follows, using a kit (Beyotime, product number: S0109):

[0057] (a) Preparation of NBT / enzyme working solution: Prepare an appropriate amount of NBT / enzyme working solution according to a volume of 160 μL for each reaction.

[0058] Mix 158 μL of SOD detection buffer, 1 μL of NBT, and 1 μL of enzyme solution evenly to prepare a 160 μL NBT / enzyme working solution. Prepare an appropriate amount of NBT / enzyme working solution according to the number of samples to be tested (including standards).

[0059] (b) Preparation of the reaction initiation working solution: Dissolve and mix the reaction initiation solution (40X) from the kit (Beyotime, product number: S0109). Dilute the solution by adding 39 μL of SOD detection buffer to every 1 μL of reaction initiation solution (40X). Mix well to obtain the reaction initiation working solution. Prepare an appropriate amount of reaction initiation working solution according to the number of samples to be tested (including standards). Store the prepared reaction initiation working solution at 4°C or on ice. It can be used on the same day, but it is recommended to prepare and use it immediately.

[0060] (c) Sample determination: Refer to the table below to set up sample wells and various blank control wells using a 96-well plate. Add the test samples and other solutions in the order listed in the table below. After adding the reaction start-up working solution, mix thoroughly. React at 37°C for 30 min, and measure the absorbance at 560 nm.

[0061] Table 1. Preparation of SOD enzyme activation solution

[0062]

[0063] Calculation of total SOD activity in the test sample: Inhibition percentage = [(A blank control 1 - A blank control 2) - (A test sample - A blank control 3)] / (A blank control 1 - A blank control 2) × 100%

[0064] In the detection system, the SOD enzyme activity unit = inhibition percentage / (1 - inhibition percentage) units.

[0065] As shown in Table 2 below, the main optimization of Comparative Examples 1-5 was the effect of the mass ratio of chitosan to sodium chondroitin sulfate A (the mass concentration of sodium chondroitin sulfate A in dispersion system C was fixed at 1.5% during the optimization process. Since the concentration of chitosan solution was concentrated to 1.5-15% in step (1), the ratio of dispersion system B and dispersion system A also needed to be adjusted accordingly so that the mass concentration of sodium chondroitin sulfate A in dispersion system C was 1.5%) on the mechanical strength, fixation ability and SOD enzyme activity of the patch. The results showed that the microneedles prepared with a mass ratio of chitosan to sodium chondroitin sulfate A of 4:1 were the best. The main optimization of Comparative Examples 1 and 6-8 was the effect of the stirring speed in step (4). The patch with the best comprehensive performance was obtained with a stirring speed of 1000-2000 rpm. The main optimization of Comparative Examples 1 and 9-12 was the effect of the number of repetitions in steps (7) and (8). When the number of repetitions was 2 or more, the performance of the patch was not significantly different. After comprehensive comparison, the optimal comprehensive performance of the patch, including mechanical strength, skin fixation ability and enzyme activity of active ingredient SOD, is achieved when the mass ratio of chitosan to chondroitin sulfate sodium salt is 4:1, the stirring speed in step (4) is 1000-2000 rpm, and the number of repetitions of steps (7) and (8) is 2-4 times.

[0066] Table 2 Optimization of the manufacturing method for SOD-containing patches

[0067]

[0068]

[0069] Example 2: The therapeutic effect of SOD-containing patches on a rat model of hyperuricemia.

[0070] The patches were prepared according to steps (1)-(9) described in Example 1 and the dosage ratio, rotation speed, and number of repetitions of Comparative Example 1. The components in the patches were replaced with those listed in Table 3 to prepare different SOD-containing patches. One hundred ordinary male SD rats, weighing (200±20) g and aged 6–8 weeks, were randomly divided into 10 groups (n=10 per group) based on their serum uric acid levels: blank group, negative control group, Comparative Example 1, and rats 13–19. The blank group was fed a standard diet, while the other groups were given adenine at a dose of 100 mg·b·w / kg added to their diet for 32 days to induce modeling. After 32 days, the patches prepared according to Table 3 were administered. One patch was administered every two days for a total of eight administrations. One day before drug administration (considered day 0), 100 μl of venous blood was collected from each group of rats. Blood was then collected every 8 days thereafter. Serum was separated by centrifugation, and the uric acid (UA) content in the serum was determined using a uric acid (UA) test kit (enzyme colorimetric method) (microplate method, sourced from Nanjing Jiancheng Bioengineering Research Institute Co., Ltd.).

[0071] Instructions for using the patch: Remove the hair from the back of the rat, insert the patch vertically into the skin on the back, and gently press for 2-3 minutes. The patch will then adhere firmly to the skin. Remove the patch after 24 hours.

[0072] Table 3. Ingredients of SOD-containing patches

[0073]

[0074] The results are as follows Figure 2 As shown, at day 8, the serum uric acid level in the model group was the highest, while the uric acid levels in the other treatment groups were lower than those in the negative control group. At day 16, serum uric acid levels in all groups decreased. Comparison of the negative control group and control groups 1, 16, 17, 18, and 19 revealed no significant difference in serum uric acid levels between the negative control and control group 16, but significant differences between the negative control and control groups 1, 17, 18, and 19 (P < 0.05). This indicates that 250 IU-2000 IU SOD patches significantly reduce serum uric acid levels, with the effect becoming more pronounced with higher doses. Patches with SOD levels of 500 IU and above maintained uric acid levels in the model rats within the normal range, showing no significant difference from the control group.

[0075] On the other hand, by comparing and optimizing Comparative Example 15 with Comparative Examples 1, 13, and 14, it was found that the serum uric acid levels of Comparative Examples 1, 13, and 14 decreased significantly, and Comparative Example 1 had the best effect. This indicates that chitosan and chondroitin sulfate sodium salt serve not only as the substrate for patch molding in this invention, but also as important active ingredients for reducing uric acid.

[0076] Example 3: Therapeutic effect of SOD-containing patch on rat ankle arthritis model

[0077] One hundred male SD rats of ordinary grade, weighing (200±20) g and aged 6-8 weeks, were randomly divided into 10 groups (n=10 per group) according to their serum uric acid levels: blank group, negative control group, comparative groups 1, 13-19. Except for the blank group, all other groups were anesthetized with 10% chloral hydrate solution. 50 μL of sodium urate solution was injected into the tibiotarsal joint cavity of the right hind paw medial malleolus. A bulging of the joint capsule on the opposite side was observed, indicating successful model establishment. After model establishment, the patch prepared in Table 3 was administered twice daily for 8 days. The circumference of the right hind paw ankle joint (0.5 mm below the joint) was measured at 0, 24, 48, and 72 hours post-modeling, and the percentage increase in ankle joint circumference was calculated. The percentage increase in ankle joint circumference was calculated using the following formula:

[0078]

[0079] The results are as follows Figure 3As shown, the negative control group had the highest percentage increase in ankle circumference, while the percentage values ​​of the other treatment groups were all lower than those of the negative control group. With increasing dosing frequency, there was no significant difference in serum uric acid levels between the negative control and control group 16, but there were significant differences in the percentage increase in ankle circumference between the negative control and control groups 1, 17, 18, and 19 (P < 0.05), indicating that the 250 IU-2000 IU SOD patch has a significant anti-inflammatory effect, and the effect is more pronounced with higher doses.

[0080] On the other hand, by comparing and optimizing Comparative Example 15 with Comparative Examples 1, 13, and 14, it was found that the values ​​of Comparative Examples 1, 13, and 14 decreased significantly, and Comparative Example 1 had the best effect. This indicates that chitosan and chondroitin sulfate sodium salt serve not only as the substrate for patch molding in this invention, but also as important anti-inflammatory active ingredients.

[0081] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A SOD-containing patch for gouty arthritis, characterized in that, The SOD-containing patch is a soluble microneedle patch, comprising a base layer and an SOD-loaded needle tip layer. The needle tip layer consists of soluble microneedles arranged in an array on the base layer. The needle tip layer contains SOD, and the substrate of the needle tip layer is a chondroitin A sodium salt-chitosan polymer complex. The base layer is made of PVA film. Each microneedle is 800 μm high, with a needle tip diameter of 5-10 μm, a needle base diameter of 200 μm, and a distance of 800 μm between needle tips. The SOD enzyme activity is 981-985 IU / mL. The skin fixation ability is 24h, and the mechanical strength is 719-722 μm. The method for preparing the SOD-containing patch includes the following steps: (1) Add chitosan to an aqueous acetic acid solution, stir and mix at room temperature, dialyze for 6-8 h to bring the pH of the solution to 5.2-5.4, and concentrate the solution to a concentration of 1.5-15% for the chitosan; the concentration of the aqueous acetic acid solution is 1%. w / v The ratio of chitosan to acetic acid aqueous solution is 2%. w / v ; (2) After mixing the Tween emulsifier and the polyglycerol emulsifier, add them to the above chitosan solution and stir evenly to obtain dispersion system A; the Tween emulsifier is Tween 80; the polyglycerol emulsifier is decaglycerol monooleate; (3) Add chondroitin sulfate A sodium salt to sterile water and stir to disperse evenly to obtain dispersion system B; (4) At a stirring speed of 1000 rpm, dispersion system B was slowly added dropwise to dispersion system A, and the mixture was stirred at room temperature for 2-3 hours to obtain dispersion system C; the final proportion of chondroitin sulfate A sodium salt in dispersion system C was 1.5% w / v. (5) Weigh 1 g SOD, dissolve it in 1 mL of sterile water, add it to 1 mL of dispersion system C, and continue stirring for 1 h to obtain needle tip dispersion D; (6) Pour the above dispersion D into the microneedle mold, distribute it evenly, and make the thickness 0.05-0.15 mm; (7) Place the mold in a dry environment at 30-50℃ for 4-6 hours; (8) Remove the mold and place it at room temperature, add dispersion D again, and centrifuge; (9) Repeat steps (7) and (8) 2-4 times; remove the mold, cover the base layer, and finally peel off to obtain an SOD-containing patch for gouty arthritis; The microneedle substrate is composed of chitosan and sodium chondroitin sulfate A in a mass ratio of 4:1; the degree of deacetylation of chitosan is ≥95%, and the viscosity is 100-200 mpa.s; the specific activity of SOD is 50,000 IU / g.

2. The SOD-containing patch for gouty arthritis according to claim 1, characterized in that, Including the following steps: (1) Add 2 g of chitosan to 100 mL of 1% acetic acid aqueous solution, stir and mix at room temperature, dialyze for 6-8 h to make the pH of the solution 5.2-5.4, and concentrate the concentration of chitosan solution to 1.5-15% by rotary evaporation under reduced pressure; (2) After heating and mixing 12 mg Tween-80 and 3 mg decaglycerol monooleate, add them to the above chitosan solution and stir evenly to obtain dispersion system A; (3) Weigh chondroitin sulfate A sodium salt, add it to 5 mL of sterile water, stir and disperse evenly to obtain dispersion system B; (4) At a stirring speed of 1000 rpm, dispersion system B was slowly added dropwise to dispersion system A, and stirred at room temperature for 2-3 hours to obtain dispersion system C; the mass concentration of chondroitin A sodium salt in dispersion system C was 1.5%; (5) Weigh 1 g SOD, dissolve it in 1 mL of sterile water, add it to 1 mL of dispersion system C, and continue stirring for 1 h to obtain needle tip dispersion D; (6) Pour the above dispersion D into the microneedle mold, distribute it evenly, and make the thickness 0.05-0.15 mm; (7) Place the mold in a dry environment at 30-50℃ for 4-6 hours; (8) Remove the mold and place it at room temperature. Add dispersion D again and centrifuge at 2000 g for 20 min. (9) Repeat steps (7) and (8) twice, remove the above mold, cover the base layer, and finally peel off to obtain the SOD-containing patch for gouty arthritis; The mass ratio of chitosan to chondroitin A sodium salt is 4:1; the degree of deacetylation of chitosan is ≥95%, and the viscosity is 100-200 mpa.s; the specific activity of SOD is 50,000 IU / g.

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