Gel patch with refined aluminum hydroxide as cross-linking agent and its preparation

Abstract

This invention relates to a gel patch using aluminum hydroxide as a crosslinking agent and its preparation. The gel patch of this invention comprises a drug-containing plaster layer, including a main drug and excipients, wherein the excipients include aluminum hydroxide. The gel patch of this invention has a smooth surface, strong adhesion, good biocompatibility, leaves no residue after repeated application and removal, and can slowly release the loaded drug. It overcomes the problems of excessive hardness, over-crosslinking, excessive elasticity, and insufficient adhesion caused by conventional aluminum salt crosslinking agents. Using aluminum hydroxide as a crosslinking agent, compared with traditional crosslinking agents such as aluminum hydroxide, aluminum chloride, and aluminum hydroxide, the prepared gel patch has advantages such as stable molding, intact appearance, good spreadability, strong adhesion, and good skin adhesion. Moreover, it has stable performance during long-term storage and significantly improves efficacy.

Description

Technical Field

[0001] This invention discloses a method for synthesizing a novel excipient, refined aluminum hydroxide, and for preparing a gel patch using refined aluminum hydroxide as a crosslinking agent, belonging to the technical field of external gel patches. Background Technology

[0002] Gel patches are a commonly used form of topical drug delivery. Also known as poultices, gel patches are plasters made by mixing medicinal extracts, decoction pieces, or chemical drugs with a suitable hydrophilic matrix and then applying the mixture to a backing material. Gel patches originated from early mud-based application agents. With advancements in pharmaceutical excipients, modern gel patches use water-soluble polymers as the matrix, evolving from non-crosslinked to crosslinked types, effectively solving problems such as weak cohesion, insufficient viscoelasticity, and poor moisture retention.

[0003] Gel patches consist of three parts: an anti-adhesive layer, a paste, and a backing layer. The paste is the key component, playing a decisive role in the formulation's properties, drug content, adhesiveness, and therapeutic effect. The paste contains numerous components, including matrix materials, thickeners, cross-linking agents, moisturizers, fillers, skin penetration enhancers, purified water, and other additives. The matrix materials of gel patches include sodium polyacrylate, polyvinyl alcohol, chitosan, and carbomer. Cross-linking agents are typically high-valence metal ions, such as aluminum salts (aluminum hydroxyl, aluminum chloride, aluminum hydroxide, etc.), which cross-link with the carboxyl and hydroxyl groups in the matrix to form a cross-linked matrix. As the amount of cross-linking agent increases, cohesion and initial tack improve; however, excessive use leads to over-cross-linking, resulting in an overly hard paste with reduced viscosity; insufficient use results in inadequate cross-linking and poor cohesion. While these aluminum salt cross-linking agents impart shapeability to the gel patch, they also contribute to a harder paste and insufficient viscosity.

[0004] Chinese patent document CN107569627A discloses a method for preparing a pediatric diarrhea gel patch. It utilizes aluminum chloride to promote the cross-linking of a carbomer matrix and employs the reaction of citric acid with aluminum ions to form a cyclic complex, adjusting the cross-linking strength to achieve a patch with moderate softness and firmness suitable for children. However, the gel patch matrix using aluminum chloride as a cross-linking agent exhibits poor uniformity and sometimes clumps, which is inferior to using aluminum hydroxide as a cross-linking agent. Chinese patent document CN110946846B discloses a method for preparing a loxoprofen sodium gel ointment using aluminum hydroxide as a cross-linking agent. This method offers advantages such as stable molding, intact appearance, good transdermal absorption, non-allergenic and non-irritating properties, and resistance to mold growth. However, it suffers from low adhesion, failing to achieve satisfactory results. Patents such as CN104546803A, CN114010685A, and CN117731595A also disclose methods for preparing gel plasters using aluminum hydroxide as a crosslinking agent, but all of them fail to achieve satisfactory results due to low initial adhesion.

[0005] Currently, common problems with topical patches include: poor adhesion and short shelf life, decreased adhesion after repeated application and removal, poor skin compatibility, and skin residue. This invention, through multiple experiments, has found that using aluminum hydroxide as a cross-linking agent in gel patches can improve their properties, resulting in stable patch formation, intact appearance, good spreadability, high adhesion, and good skin adherence, thereby achieving better therapeutic effects and improving patient compliance.

[0006] Dubovoy et al. (Dubovoy, V., Subramanyam, R., Stranick, M., Du-Thumm, L., Pan, L. Facile Preparation of Ultrafine Aluminum Hydroxide Particles with or without Mesoporous MCM-41 in Ambient Environments[J]. Journal of Visualized Experiments, 2017(123)) titrated aluminum ions to pH 4.6 with arginine and separated and purified the product by gel permeation chromatography (GPC) to remove arginine, obtaining gibbsite crystal particles with a particle size of about 10-30 nm. NaCl was then added to aggregate the nanoparticles into large-particle-size Al(OH)3 precipitates, or the size of aluminum hydroxide particles was limited by the pore size of MCM-41 mesoporous silica material to obtain Al-MCM-41 composite materials. We were surprised to find that by modifying the synthesis process and using dialysis to remove counterions, followed by further concentration, we obtained a homogeneous gel containing arginine. This gel, acting as a crosslinking agent, can effectively and rapidly crosslink partially neutralized sodium polyacrylate to prepare a gel patch. We call this arginine-containing aluminum hydroxide gel "arginine-hydroxyaluminum," which consists of amorphous nanoparticles composed of aluminum hydroxide and arginine. Under acidic conditions of tartaric acid, it releases trivalent aluminum ions, which act as crosslinking agents, crosslinking with carboxyl functional groups in the backbone. This process allows us to prepare a gel patch using arginine-hydroxyaluminum as a crosslinking agent. We prepared arginine-hydroxyaluminum by reacting aluminum salt solutions with arginine within a specific pH range. Compared to traditional crosslinking agents such as galacto-hydroxyaluminum and aluminum hydroxide, the patch prepared using arginine-hydroxyaluminum as a crosslinking agent exhibits better adhesion, superior viscosity, and greater stability. Summary of the Invention

[0007] The applicant discovered that arginine-containing aluminum hydroxide, prepared by reacting aluminum salts with arginine, can improve the properties of gel patches by acting as a crosslinking agent, resulting in stable patch formation, intact appearance, good spreadability, high viscosity, and good skin adherence, thereby achieving better therapeutic effects. The specific invention is as follows:

[0008] A gel patch comprising an active pharmaceutical ingredient (API) and excipients, wherein the excipients include a crosslinking agent, the crosslinking agent being aluminum hydroxide.

[0009] The gel patch of the present invention includes a backing layer, a medicated paste layer and an anti-adhesive layer, wherein the medicated paste layer includes: an active pharmaceutical ingredient (API), a thickener, a matrix material, a crosslinking agent, a crosslinking regulator, a filler, a humectant and purified water, wherein the crosslinking agent is purified aluminum hydroxide.

[0010] The amount of hydroxyaluminate used is 0.05% to 5% of the weight of the drug-containing gel matrix, preferably 0.3% to 0.6%. The drug-containing gel matrix is ​​the same as the medicated ointment layer.

[0011] The gel plaster of this invention comprises a tackifier selected from at least one of gelatin, povidone K90, carbomer 934, and carbomer 940. The skeleton material comprises a polymer selected from at least one of polyacrylic acid, povidone, polyvinyl alcohol, carbomer, sodium carboxymethyl cellulose, and methylcellulose. The crosslinking regulator is selected from at least one of tartaric acid, citric acid, or EDTA-2Na. The filler is selected from at least one of micronized silica gel, zinc oxide, diatomaceous earth, calcium carbonate, titanium dioxide, or kaolin. The moisturizer is selected from at least one of sorbitol, propylene glycol, polyethylene glycol, or glycerin.

[0012] The gel patch of the present invention, wherein the refined aluminum hydroxide is prepared by the following method:

[0013] (1) Under continuous heating and stirring conditions, use a constant flow pump to add alkaline solution to the aluminum salt solution at a certain flow rate until the pH of the system is maintained between 3.0 and 6.0;

[0014] (2) After the pH stabilizes, add arginine to the system. The molar ratio of arginine to aluminum salt is 0.5 to 2.5:1. Continue to react at the original temperature and stirring speed.

[0015] (3) Dialyze the solution after the reaction to remove unreacted impurities.

[0016] In step (1), the aluminum salt is selected from AlCl3·6H2O, aluminum sulfate or potassium aluminum sulfate dodecahydrate, and the aluminum ion concentration is 0.5-5M; the alkali in step (1) is selected from sodium hydroxide, potassium oxide, ammonia or urea, and the concentration is 2.0%-20%; the heating temperature in step (1) is 30℃-100℃, and the reaction time in step (2) is 12-72h.

[0017] The gel patch of the present invention includes a preparation method comprising the steps of preparing an aqueous phase, preparing an oil phase, preparing a main drug phase, and then mixing the aqueous phase, oil phase, and main drug phase; wherein:

[0018] The aqueous phase components are selected from: gelatin, tartaric acid, polyvinyl alcohol, and EDTA 2Na.

[0019] The oil phase components are selected from: sodium carboxymethyl cellulose, sodium polyacrylate (NP)-700, titanium dioxide, propylene glycol, polyethylene glycol, and glycerin.

[0020] The active pharmaceutical ingredient (API) in the active pharmaceutical ingredient (API) may include, but is not limited to: flurbiprofen, loxoprofen sodium, lidocaine, indomethacin, diclofenac, etc.; other components in the API may be selected from: Span 83, Tween 80, clomiphene, polylactic acid menthol, polyacrylic acid solution.

[0021] Among them, aluminum hydroxide can exist in any phase, such as as an aqueous phase component, an oil phase component, or a main drug phase component.

[0022] The gel patch of the present invention can be prepared by the following method: Weigh aluminum hydroxide and dissolve at least one component selected from gelatin, tartaric acid, polyvinyl alcohol, and EDTA-2Na in purified water in a certain proportion. After mixing, an aqueous phase is obtained. Mix at least two components selected from sodium carboxymethyl cellulose, sodium polyacrylate (NP)-700, titanium dioxide, propylene glycol, polyethylene glycol, and glycerin in a certain proportion to form an oil phase. Stir at least two components selected from Span 83, Tween 80, crombutin, the active ingredient, and polylactic acid menthol evenly. Add polyacrylic acid solution to the mixture to obtain the active ingredient phase. After mixing the three phases, stir evenly and coat the mixture onto a non-woven fabric at room temperature. Cover with an anti-adhesive layer to obtain the gel patch.

[0023] The preferred formulation of the gel patch of the present invention is as follows:

[0024] Active pharmaceutical ingredient 0.1 wt% to 10 wt%

[0025] Skeleton material 1 wt% ~ 10 wt%

[0026] Filler 1 wt% to 10 wt%

[0027] Tackifier 2 wt% to 10 wt%

[0028] Aluminum hydroxide 0.1 wt% to 1 wt%

[0029] Crosslinking regulator 0.1 wt% to 1 wt%

[0030] Moisturizer 20 wt% ~ 40 wt%

[0031] Skin penetration enhancer 0.1 wt% to 6 wt%

[0032] The most preferred formulation of the gel patch of the present invention is as follows:

[0033] Aqueous phase

[0034] 3wt% gelatin

[0035] 0.5wt% tartaric acid

[0036] 2wt% Polyvinyl alcohol

[0037] 0.22wt% EDTA-2Na 0.15wt% Refined Aluminum Hydroxide

[0038] 42.82wt% purified water

[0039] oil phase

[0040] 4wt% Sodium Carboxymethyl Cellulose

[0041] 6wt% NP-700

[0042] 1wt% Kaolin

[0043] 0.25wt% titanium dioxide

[0044] 28wt% glycerin

[0045] Main drug phase

[0046] 0.3wt% Flurbiprofen

[0047] 0.05wt% Span 83

[0048] 0.5wt% Tween 80

[0049] 0.5wt% Cromite

[0050] 0.5wt% Isopropyl Myristate

[0051] 0.2wt% L-Menthol

[0052] 0.01wt% menthol lactate

[0053] 10wt% polyacrylic acid

[0054] The thickness of the medicated ointment layer described in this invention can range from 100 to 2000 μm, preferably from 500 to 1000 μm.

[0055] The backing layer of this invention is preferably made of a material that can support the ointment layer, has high flexibility, good extensibility, good breathability, and low irritation. It can be selected from at least one of woven fabric, non-woven fabric, plastic film, paper, and rayon. The protective film of this invention can be selected from at least one of polyester, polyurethane, polyethylene, and polypropylene. Beneficial effects: This invention uses aluminum hydroxyaluminate prepared by reacting aluminum salt with arginine as a crosslinking agent for gel patches, which can improve the properties of the gel patches, making the ointment stable in shape, intact in appearance, with good spreadability, high viscosity, and good skin adherence. This avoids the problem of the patch loosening or failing to adhere during use, thereby achieving better therapeutic effects.

[0056] In this invention, the gel plaster uses refined aluminum hydroxide as a crosslinking agent and a hydrophilic polymer material with high safety and good viscosity as a skeleton, supplemented by fillers, moisturizers, thickeners, etc., to produce a smooth and delicate plaster with excellent viscosity, no residue after repeated application and removal, good biocompatibility, and good application prospects. Attached Figure Description

[0057] Figure 1 Fourier transform infrared (FTIR) spectrum of purified aluminum hydroxyl;

[0058] Figure 2 X-ray powder diffraction (XRD) pattern of refined aluminum hydroxide;

[0059] Figure 3 Differential scanning calorimetry (DSC) curve of refined aluminum hydroxide;

[0060] Figure 4 Thermogravimetric analysis (TGA) curve of refined aluminum hydroxide;

[0061] Figure 5 Frequency scanning of aluminum hydroxide and aluminum hydroxide pastes;

[0062] Figure 6 Temperature scanning of aluminum hydroxide and aluminum hydroxide pastes;

[0063] Figure 7 Amplitude scanning of aluminum hydroxide and aluminum hydroxyl pastes;

[0064] Figure 8 Creatalization scanning of aluminum hydroxyl and aluminum hydroxyl pastes; Detailed Implementation

[0065] The present invention will be further illustrated by the following examples and test cases, but is not limited thereto.

[0066] Example 1

[0067] (1) Weigh a certain amount of AlCl3·6H2O and dissolve it in purified water to prepare an aluminum ion solution with a concentration of 0.9M. Measure ammonia water with a concentration of 25-28%, add 3 times the volume of purified water to dilute it, mix well, and prepare an ammonia water solution with a concentration of 6.25-7%.

[0068] (2) Add ammonia solution dropwise to aluminum salt solution under stirring at 60℃ until the pH is 3.0 to 6.0, then stop adding arginine. The molar ratio of arginine to aluminum ions is 1:1.83. The reaction is carried out for 48 hours.

[0069] (3) After the reaction is complete, dialyze the solution for 24 hours, and then concentrate the sample solution obtained after dialyze by ultrafiltration to the required concentration. The aluminum content is determined according to the 2020 edition of the Chinese Pharmacopoeia, Part III, General Chapter <3106 Determination of Aluminum Hydroxide (or Aluminum Phosphate)>.

[0070] Example 2

[0071] First, add 3 wt% gelatin to an appropriate amount of purified water, record the initial weight, and after complete swelling in an 80℃ water bath, weigh and add purified water. Dissolve the gelatin in 0.5 wt% tartaric acid. Next, add 2 wt% polyvinyl alcohol to an appropriate amount of purified water, record the initial weight, and after complete swelling in an 80℃ water bath, weigh and add purified water. Dissolve the polyvinyl alcohol in 0.22 wt% EDTA-2Na and 0.15 wt% purified aluminum hydroxide. Combine the gelatin and polyvinyl alcohol solutions to form the aqueous phase. Mix 4 wt% sodium carboxymethyl cellulose, 6 wt% NP-700, 1 wt% kaolin, 0.25 wt% titanium dioxide, and 28 wt% glycerol to form the oil phase. The API phase was prepared by mixing 0.05 wt% Span 83, 0.5 wt% Tween 80, 0.5 wt% Clomidon, 0.5 wt% Isopropyl Myristate, 0.3 wt% Flurbiprofen, 0.2 wt% L-Menthol, 0.01 wt% Menthol Lactate, and 10 wt% Polyacrylic Acid. The aqueous phase, oil phase, and API phase were then mixed and stirred rapidly for 4 minutes. This mixture was then applied to a nonwoven fabric at room temperature, and a release liner was applied to obtain the gel patch.

[0072] Example 3

[0073] A mixture of 15 wt% glycerol, 5 wt% acrylic starch 300, 9 wt% talc, 0.5 wt% sodium carboxymethyl cellulose, 0.25 wt% titanium dioxide, and 5.5 wt% NP-700 was used as the oil phase. A mixture of 15 wt% glycerol, 1.134 wt% loxoprofen sodium, 0.4 wt% polysorbate, 2 wt% clomiphene, 0.005 wt% disodium edetate, and 0.18 wt% purified aluminum hydroxide was used as the API phase. A mixture of 1.2 wt% tartaric acid, purified water, and 7 wt% resin emulsion was used as the aqueous phase. The oil, aqueous, and API phases were then mixed, coated onto a non-woven fabric, and covered with an anti-adhesive layer to obtain the gel patch. Example 1: Fourier transform infrared spectroscopy analysis of purified aluminum hydroxide.

[0074] The Fourier transform infrared (FTIR) spectra of the refined aluminum hydroxyl excipient were measured using the potassium bromide tableting method. Based on the FTIR spectra, the prepared refined aluminum hydroxyl and the commercial aluminum hydroxyl excipient showed a peak value of 1653.23 cm⁻¹. -1 and 1644.2cm -1 All peaks were observed at 668.54 cm⁻¹, all of which were ester carbonyl peaks. Simultaneously, the purified aluminum hydroxyl peak was observed at 668.54 cm⁻¹. -1 The appearance of the Al-N stretching vibration peak at 1653.23 cm⁻¹ confirms the cross-linking reaction between aluminum atoms and arginine. The peak at arginine-hydroxyaluminum is also observed at 1653.23 cm⁻¹. -1 and 1675.58cm -1 The split peak may be due to the interaction between the carbonyl group of polyacrylic acid and the arginine carbonyl group, which have similar frequencies, causing the peak to split.

[0075] X-ray powder diffraction analysis of purified aluminum hydroxide in Experimental Example 2

[0076] The prepared refined aluminum hydroxide is a white powdery solid, and no obvious flocculent precipitate is found in aqueous solution. Compared with hydroxyaluminate, refined aluminum hydroxide has a smaller particle size and larger interplanar spacing. A broad peak is found at 2θ = 18.65° in the diffraction pattern, indicating that the prepared refined aluminum hydroxide is in an amorphous state.

[0077] Thermodynamic Analysis of Experimental Example 3: Refined Aluminum Hydroxide

[0078] DSC (Disseminated Scaling) utilizes the unique thermodynamic properties of different crystalline forms of a test sample, identifying the crystalline state by observing changes in parameters such as the number, position, shape, and amount of heat absorbed by endothermic or exothermic peaks. TGA (Thermal Gauge Analysis) utilizes the unique mass-weight loss percentage versus temperature parameter of different crystalline forms of a test sample to identify the crystalline state.

[0079] A suitable amount of the test sample was weighed and measured on a simultaneous thermal analyzer at a heating rate of 10 K / min. The DSC curve showed a strong exothermic peak at 207.5℃, formed by the oxidative decomposition of purified aluminum hydroxyl, and an endothermic peak at 205.9℃. Simultaneously, a weight loss plateau was observed on the TGA curve, with a weight loss rate of 9.55%, indicating approximately 9.55% water of crystallization. At 500℃, the weight loss became constant, with a residual mass of approximately 59.7% of the original mass.

[0080] Test Example 4

[0081] Unless otherwise specified, the initial tack, holding tack, and adhesion of gel patches shall be determined according to the 2020 edition of the Chinese Pharmacopoeia, Part IV, General Chapter <0952 Adhesion Determination Method>, as follows:

[0082] Initial tack: The initial tack of the plaster was determined using the rolling ball ramp stop method. A series of steel balls of appropriate size were rolled over the tack surface of the test sample placed on an inclined plate. The tack was evaluated based on the largest steel ball that the test sample could adhere to. In Example 2, the largest steel balls adhered to by the aluminum hydroxide gel plasters were 24 and 19, respectively. In Example 3, the largest steel balls adhered to by the aluminum hydroxide gel plasters were 25 and 21, respectively. The initial tack of the aluminum hydroxide gel plaster was significantly greater than that of the aluminum hydroxide gel plaster.

[0083] Adhesion holding power: The adhesive side of the test sample is adhered to the surface of the test plate and placed vertically. A weight of a specified mass is suspended along the length of the test sample, and the time (s) of the sample falling or the distance (cm) displaced within one hour is recorded. The test results show that the refined aluminum hydroxide gel patch has a longer suspension time than the hydroxyaluminum hydroxide gel patch, and the refined aluminum hydroxide gel patch moves a smaller distance within a certain time, indicating better adhesion holding power.

[0084] Adhesion: The test sample was flattened and adhered to the base plate, and after fixation, an appropriate test mode was selected for measurement. The results all showed that the aluminum hydroxide gel patch had greater adhesion than the aluminum hydroxide gel patch.

[0085] Table 1. Holding power and adhesion of aluminum hydroxide and aluminum hydroxide paste in Example 2

[0086]

[0087] Table 2. Holding power and adhesion of aluminum hydroxide and aluminum hydroxide paste in Example 3

[0088]

[0089] Experimental Example 5: Rheological Test of Gel Patch

[0090] Instrument: Discovery HR-2 rheometer.

[0091] Parameter settings:

[0092] (1) Frequency scan: Angular frequency: 0.1rad / s~100rad / s; Temperature: 25℃.

[0093] (2) Temperature scan: Temperature: 25℃~45℃; Angular frequency: 10rad / s.

[0094] (3) Amplitude scan: Temperature: 25℃; Angular frequency: 6.28319rad / s.

[0095] (4) Creep scan: Temperature: 25℃; Gap: 600μm.

[0096] Rheological tests were conducted on the gel patch obtained in Example 2. The frequency scanning results showed that the viscous modulus of the aluminum hydroxide paste at an angular frequency of 0.1 rad / s and the elastic modulus of the aluminum hydroxide paste at an angular frequency of 100 rad / s were both greater than those of the aluminum hydroxide paste, indicating that it has excellent initial tack, peel strength and cohesive force.

[0097] As temperature rises, the elastic modulus and viscous modulus of the paste decrease, while the tanδ (tanδ = viscous modulus / elastic modulus) value continuously increases. This phenomenon is because as temperature increases, the thermal motion of molecules increases, leading to the disruption of the network structure between polymer chains. Figure 7 It can be seen that the refined aluminum hydroxide paste has a relatively high tanδ value, exhibiting better ductility at the same temperature, making it more suitable for coating. In amplitude scanning, the tanδ value of refined aluminum hydroxide is greater than that of aluminum hydroxyl, indicating that the adhesiveness of refined aluminum hydroxide paste is superior to that of aluminum hydroxyl plaster, and it also has a wider linear region and better stability. Creep scan diagram ( Figure 8 The results show that the J(t) value of the refined aluminum hydroxide paste is more stable, indicating that it is not easily deformed, has good shape retention, and is more stable during use.

Claims

1. A gel patch, comprising an active pharmaceutical ingredient and excipients, wherein the excipients include a crosslinking agent, the crosslinking agent being refined aluminum hydroxide, and the refined aluminum hydroxide is prepared by the following method: (1) Under continuous heating and stirring conditions, use a constant flow pump to add alkaline solution to the aluminum salt solution at a certain flow rate until the pH of the system is maintained between 3.0 and 6.0; (2) After the pH stabilizes, add arginine to the system. The molar ratio of arginine to aluminum salt is 0.5~2.5:

1. Continue to react at the original temperature and stirring speed. (3) Dialyze the solution after the reaction to remove unreacted impurities.

2. The gel plaster according to claim 1, wherein the refined aluminum hydroxide is prepared by the following method: the aluminum salt in step (1) is selected from: AlCl3·6H2O, aluminum sulfate or potassium aluminum sulfate dodecahydrate, and the aluminum ion concentration is 0.5~5 M; the alkali in step (1) is selected from: sodium hydroxide, potassium oxide, ammonia or urea, and the concentration is 2.0%~20%; the heating temperature in step (1) is 30℃~100℃, and the reaction time in step (2) is 12~72 h.

3. The gel patch according to any one of claims 1 or 2, further comprising a backing layer, a medicated paste layer, and an anti-adhesive layer, wherein, The medicated ointment layer comprises: the active ingredient, a thickener, a matrix material, a crosslinking agent, a crosslinking regulator, a filler, a humectant, and purified water.

4. The gel patch according to claim 3, characterized in that: The thickener is selected from at least one of gelatin, povidone K90, carbomer 934, and carbomer 940.

5. The gel patch according to claim 3, characterized in that: The skeleton material is selected from at least one of the following: polyacrylic acid, povidone, polyvinyl alcohol, carbomer, sodium carboxymethyl cellulose, and methyl cellulose; the crosslinking regulator is selected from at least one of tartaric acid, citric acid, or EDTA-2Na; the filler is selected from at least one of micronized silica gel, zinc oxide, diatomaceous earth, calcium carbonate, titanium dioxide, or kaolin; and the humectant is selected from at least one of sorbitol, propylene glycol, polyethylene glycol, or glycerin.

6. The gel patch according to claim 3, characterized in that: The preparation method of the ointment-containing layer includes the steps of preparing an aqueous phase, preparing an oil phase, preparing a main drug phase, and then mixing the aqueous phase, oil phase, and main drug phase; wherein: The aqueous phase components are selected from: gelatin, tartaric acid, polyvinyl alcohol, and EDTA 2Na; The oil phase components are selected from: sodium carboxymethyl cellulose, sodium polyacrylate (NP)-700, titanium dioxide, propylene glycol, polyethylene glycol, and glycerin; The active pharmaceutical ingredient in the active pharmaceutical ingredient phase is selected from: flurbiprofen, loxoprofen sodium, lidocaine, indomethacin, and diclofenac; other components in the active pharmaceutical ingredient phase are selected from: Span 83, Tween 80, clomiphene, polylactic acid menthol, and polyacrylic acid solution; among them, aluminum hydroxide can be present in any phase.

7. The method for preparing the gel patch according to claim 6, characterized in that: Weigh out refined aluminum hydroxide and add at least one component selected from gelatin, tartaric acid, polyvinyl alcohol, and EDTA-2Na in proportion to purified water. Mix well to obtain an aqueous phase. Mix at least two components selected from sodium carboxymethyl cellulose, sodium polyacrylate (NP)-700, titanium dioxide, propylene glycol, polyethylene glycol, and glycerin in proportion to obtain an oil phase. Stir at least two components selected from Span 83, Tween 80, crombutin, the active ingredient, and polylactic acid menthol to obtain a drug phase. Add polyacrylic acid solution to the mixture to obtain the active ingredient phase. Mix the three phases and stir well. Coat the mixture onto a nonwoven fabric at room temperature and cover with an anti-stick layer to obtain the final product.

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