Use of polymethacryloyloxyethyltrimethylammonium chloride as an adhesive for the gel patch plaster

Abstract

The present application provides a polymer of a compound shown in formula I, or a copolymer of the compound shown in formula I as a monomer and a monomer containing a carbon-carbon double bond as an adhesive of a gel patch adhesive ointment layer. The gel patch adhesive ointment prepared by the present application has excellent adhesion, good compatibility with the active drug brivaracetam, and good drug release behavior, and has a wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparations, specifically relating to the use of polymethacryloyloxyethyltrimethylammonium chloride as an adhesive for the paste layer of gel patches. Background Technology

[0002] Transdermal drug delivery systems refer to a route of drug administration that delivers medication through the skin to achieve local or systemic therapeutic purposes. It is the third largest drug delivery system after oral and injectable administration, and has enormous potential market prospects. Currently, there are two main types of marketed transdermal drug delivery formulations: pressure-sensitive adhesive patches and gel patches. In addition to the common advantages of transdermal drug delivery formulations, such as reduced fluctuations in blood drug concentration, reduced toxic side effects, convenient administration, and good patient compliance, gel patches have the following characteristics compared to traditional transdermal drug delivery formulations: they do not contain organic solvents or other highly irritating ingredients, resulting in good skin compatibility; they have a large drug loading capacity; they can improve the hydration of the stratum corneum, promoting drug penetration and increasing bioavailability; they are convenient to use, do not stain clothing, and can be repeatedly applied.

[0003] According to the definition of gel patches in the 2020 edition of the Chinese Pharmacopoeia, gel patches mainly consist of three parts: the raw drug, the hydrophilic matrix, and the backing material. The characteristics of the hydrophilic matrix not only determine its transdermal permeability, moisturizing properties, adhesion, safety, and comfort, but also the overall quality of the gel patch. The hydrophilic matrix mainly consists of adhesives, fillers, humectants, and transdermal penetration enhancers. Adhesives not only give the patch its viscosity but are also the main substances supporting the formation of a network-like three-dimensional structure within the patch, generating sufficient cohesion and elastic strength, and are also the main carriers of water. As an adhesive in gel patches, it needs to have suitable adhesive force, ensuring stable adhesion to the skin without causing skin damage due to excessive adhesion during removal. Simultaneously, it needs good compatibility with the active pharmaceutical ingredient, a reasonable sustained-release rate, and ensure the achievement of the expected therapeutic effect.

[0004] Commonly used adhesives mainly include synthetic and semi-synthetic polymers (such as sodium polyacrylate, povidone, sodium carboxymethyl cellulose, carbomer, etc.) and natural polymers (such as gelatin, astragalus gum, agar, etc.). Currently, the most studied skeleton materials are mainly different types of sodium polyacrylate (such as NP700, NP800, etc.), and there are also research reports on the use of synthetic, semi-synthetic and natural polymers in appropriate proportions.

[0005] However, when using different types of sodium polyacrylate (such as NP700, NP800, etc.) as the matrix material, in order to improve the cohesive strength of the matrix, enhance adhesion, and prevent phenomena such as peeling and cold flow of the paste, it is necessary to add crosslinking agents and crosslinking regulators to the matrix formulation. This greatly increases the difficulty of formulation research and also makes industrial production control more complex. Moreover, the use of crosslinking agents will weaken the sustained-release effect of the drug to some extent.

[0006] Therefore, it is of great significance to develop new bases for gel patches that can ensure good compatibility with drugs while also possessing excellent adhesion and drug sustained-release capabilities. Summary of the Invention

[0007] The purpose of this invention is to provide a novel brucetan gel patch with excellent adhesion and good sustained drug release performance.

[0008] The present invention provides the use of polymers of compounds of Formula I, or copolymers of compounds of Formula I as monomers with monomers containing carbon-carbon double bonds, as adhesives for the paste layer of gel plasters.

[0009]

[0010] Among them, R1, R2, R3, and R4 are each independently selected from C. 1～3 Alkyl groups; Q - It is a monovalent negative ion; n is an integer from 1 to 6.

[0011] Furthermore, R1, R2, R3, and R4 are all methyl groups; and / or n is 1.

[0012] Furthermore, the above-mentioned compound is:

[0013] Furthermore, the number-average molecular weight of the above polymer is 4 × 10⁻⁶. 7 ~5×10 7 ; and / or the weight-average molecular weight of the polymer is 4 × 10⁻⁶. 7 ~5×10 7 ; and / or the Z-average relative molecular mass of the polymer is 5.5 × 10⁻⁶. 7 ~6×10 7 .

[0014] Furthermore, the above polymer is prepared by the following method:

[0015] The monomer and initiator are dissolved in water and reacted at 30–40°C for 2–4 hours under inert gas protection, and then the temperature is raised to 45–55°C for 1–3 hours.

[0016] Furthermore, the gel patch layer described above is made from an aqueous solution containing the following mass fractions of raw materials and excipients:

[0017] The active pharmaceutical ingredient comprises 0.1–10% wt of active drug, 3–15% wt of adhesive, 1–10% wt of transdermal penetration enhancer, and 4–15% wt of humectant; the pH of the aqueous solution is 5–6.

[0018] Preferably, the gel patch layer is made from an aqueous solution containing the following mass fractions of raw materials and excipients:

[0019] Active drug 5% wt, adhesive 3-15% wt, transdermal penetration enhancer 3% wt, moisturizer 8% wt;

[0020] The preferred composition is: 5% wt of active drug, 8-12% wt of adhesive, 3% wt of transdermal penetration enhancer, and 8% wt of moisturizer.

[0021] Furthermore, the aforementioned active drug is briceracetam, ketorolac tromethorphan, flurbiprofen ester, ibuprofen, or ketoprofen, preferably briceracetam;

[0022] And / or the transdermal penetration enhancer is lauryl nitrogen. One or more of the following: ketones, propylene glycol, oxygenated terpenes such as eucalyptus oil, camphor, isopropyl myristate of eucalyptus oil, diisopropyl adipate, and 1-menthol, preferably a combination of laurocapram and propylene glycol, more preferably, wherein the mass ratio of laurocapram to propylene glycol is 2:1.

[0023] And / or the moisturizer is glycerin, polyethylene glycol, hyaluronic acid, panthenol, sorbitol or sodium alginate, preferably glycerin.

[0024] Furthermore, the above aqueous solution also contains a stabilizer and a preservative, wherein the stabilizer is a buffer pair composed of a conjugate acid and a conjugate base;

[0025] Preferably, the stabilizer is a combination of sodium hydrogen phosphate and sodium dihydrogen phosphate, a combination of acetic acid and sodium acetate, a combination of citric acid and sodium citrate, or a combination of tartaric acid and sodium tartrate; more preferably, it is a combination of sodium hydrogen phosphate and sodium dihydrogen phosphate.

[0026] The preservative is methylparaben, ethylparaben, benzyl alcohol, or benzoic acid, preferably methylparaben.

[0027] Furthermore, the amount of the stabilizer is 5-10% wt, and the amount of the preservative is 0.1-0.6% wt; preferably, the amount of the stabilizer is 7.9% wt, and the amount of the preservative is 0.5% wt.

[0028] Furthermore, the gel patch layer described above is prepared from the following raw materials in the indicated mass fractions:

[0029] The active pharmaceutical ingredient is 5% wt, the adhesive is 3-15% wt, the transdermal penetration enhancer is 3% wt, the moisturizer is 8% wt, the stabilizer is 7.9% wt, the preservative is 0.5% wt, and the balance is water.

[0030] Preferably, the gel patch is prepared from the following raw materials in the indicated mass fractions: 5% wt of active drug, 8-12% wt of adhesive, 3% wt of transdermal penetration enhancer, 8% wt of moisturizer, 7.9% wt of stabilizer, 0.5% wt of preservative, and the balance being water.

[0031] The beneficial effects of this invention: This invention develops a novel dosage form of bricetramine: a gel patch. Using polymethacryloyloxyethyltrimethylammonium chloride as the key adhesive component in the gel patch, the prepared gel patch exhibits excellent adhesion, good compatibility with the active drug bricetramine, and good sustained-release behavior, showing broad application prospects.

[0032] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0033] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0034] Figure 1 This is the infrared spectrum of polymethacryloyloxyethyltrimethylammonium chloride of the present invention.

[0035] Figure 2 This is the 1H NMR result of polymethacryloyloxyethyltrimethylammonium chloride of the present invention. Detailed Implementation

[0036] The raw materials and equipment used in this invention are all known products, obtained by purchasing commercially available products.

[0037] The polymethacryloyloxyethyltrimethylammonium chloride used in this invention was prepared by the inventor. An example method is as follows: Under nitrogen protection, an 80% aqueous solution of DMC monomer, ammonium persulfate, and tetrasodium ethylenediaminetetraacetate were reacted at a specific temperature of 35°C and stirred for 3 hours. The temperature was then raised to 50°C for 2 hours of aging. The resulting product was dissolved in water, precipitated with acetone, separated, and purified several times. The resulting flocculent material was dried and pulverized to obtain PDMC powder. The characteristic viscosity of the obtained product was 10.48 dL / g, and the monomer conversion rate was 97.74%. The reaction formula is as follows:

[0038]

[0039] The infrared spectrum of the product obtained by the above method is as follows: Figure 1 As shown; from the FTIR spectrum of DMC in the figure, 947cm -1 This corresponds to the CN stretching vibration peak of the nitrogen ion, at 1164 cm⁻¹. -1 and 1294cm -1 This corresponds to the bending vibration of CO, 1713 cm. -1 This corresponds to the stretching vibration of C=O, 1037 cm. -1 and 1632cm -1 This corresponds to the bending vibration of C=C, 3028, 2108, 1490 cm. -1 This corresponds to the stretching vibration of C=C.

[0040] From the FTIR spectrum of PDMC in the figure, it can be clearly seen that the 3028, 2108, and 1490 cm⁻¹ values ​​are related to the double bond C=C. -1 The reaction has been greatly reduced, indicating that the double bond reaction has occurred, meaning that the DMC monomer has polymerized well into PDMC, and at the same time, as at 1399 cm⁻¹ -1 A new peak appears at 1640 cm⁻¹, indicating the C-H bending vibration of the carbon atom connected to the double bond after the double bond breaks. This is because a water peak also appears at 1640 cm⁻¹. -1 Nearby, C=C also appears at 1640cm. -1 The location is nearby, so it cannot be determined whether a double bond exists there.

[0041] NMR of the product obtained by the above method 1 HNMR results are as follows Figure 2As shown in the figure, in the HNMR spectrum of DMC, the absorption peak at 6.13 is the H atom in the trans position of the methyl group in the C=C double bond, the absorption peak at 5.74 is the H atom in the cis position of the methyl group in the C=C double bond, the absorption peak at 1.91 is the H atom on the methyl group connected to the C=C double bond, the absorption peak at 4.60 is the H atom on the CH2 group connected to O, the absorption peak at 3.76 is the H atom on the CH2 group connected to N, and the absorption peak at 3.19 is the H atom on the three methyl groups connected to N. In the 1H NMR spectrum of PDMC, the solvent peak is at 4.71, the absorption peak of the H atom on the CH2 bonded to O is at 4.46, the absorption peak of the H atom on the CH2 bonded to N is at 3.78, the absorption peak of the H atom on the three methyl groups bonded to N is at 3.23, the absorption peak of the H atom after the C=C double bond is opened is at 1.98, and the absorption peak of the H atom on the methyl group bonded to the C=C double bond is at 1.05. It can be clearly seen that the intensity of the H atom peaks at positions 6.13 and 5.74 related to the C=C double bond has been greatly reduced, which indicates that the DMC monomer has been successfully polymerized into PDMC.

[0042] Gel permeation chromatography (GPC) analysis of the product obtained by the above method:

[0043] The average relative molecular mass (weight-average Mw, number-average Mn, and Z-average Mz) of this product was determined using a gel permeation chromatography (GPC-MALLS) system. The weight-average relative molecular mass of the PDMC prepared in this study was found to be 4.961 × 10⁻⁶. 7 The number-average relative molecular mass is 4.684 × 10⁻⁶. 7 The relative molecular mass of Z is 5.468 × 10⁻⁶. 7 .

[0044] The above methods are merely representative schemes for synthesizing PDMC and do not constitute a limitation on the scope of protection of this invention. Those skilled in the art can adjust and modify the above methods based on conventional technical means and common sense in the field, and synthesize PDMC with the same molecular weight through other means.

[0045] Example 1: Preparation of the gel patch matrix and corresponding gel patch of the present invention

[0046] 1) Dissolve 3g of polymethacryloyloxyethyltrimethylammonium chloride in an appropriate amount of purified water, control the water temperature at 40℃~50℃, and stir to form a uniform solution.

[0047] 2) Add 2g of lauryl nitrogen Ketone, 1g propylene glycol, 8g glycerol, 0.5g methylparaben, and 1.3g sodium hydrogen phosphate were slowly added to the solution obtained in step 1), and stirred to form a homogeneous solution.

[0048] 3) Slowly add briracetam to the solution obtained in step 2), add 6.6g of sodium dihydrogen phosphate, adjust the pH to about 5.5, add water to 100g, and stir well to obtain a solution.

[0049] 4) Apply the solution from step 3) to a non-woven fabric that has been treated with hydrophobicity using a scraping process. After laminating it with release paper, dry it in a 60°C oven for 1-3 hours, adjust the moisture content to 3%-8%, cool it, cut it, and seal it to obtain the bricetan gel patch.

[0050] Example 2: Preparation of the gel patch matrix and corresponding gel patch of the present invention

[0051] Following the preparation method of Example 1, only the amount of polymethacryloyloxyethyltrimethylammonium chloride in step 1) was increased to 8g, while the other steps remained unchanged.

[0052] Example 3: Preparation of the gel patch matrix and corresponding gel patch of the present invention

[0053] Following the preparation method of Example 1, only the amount of polymethacryloyloxyethyltrimethylammonium chloride in step 1) was increased to 12g, while the other steps remained unchanged.

[0054] Example 4: Preparation of the gel patch matrix and corresponding gel patch of the present invention

[0055] Following the preparation method of Example 1, only the amount of polymethacryloyloxyethyltrimethylammonium chloride in step 1) was increased to 15g, while the other steps remained unchanged.

[0056] The prescription compositions of Examples 1-4 are shown in Table 1:

[0057] Table 1

[0058]

[0059] Comparative Example 1: Preparation of Bericertan Gel Patch with Sodium Polyacrylate as Adhesive

[0060] 1) Disperse 8g of sodium polyacrylate NP-700, 0.3g of aluminum hydroxyl and 0.2g of tartaric acid in 8g of glycerol, and sonicate for 20-30 minutes. Then add an appropriate amount of purified water and sonicate for 20-30 minutes to form a homogeneous solution.

[0061] 2) Add 5g brucetam and 2g lauryl nitrogen. Ketone, 1g propylene glycol, 1.3g sodium hydrogen phosphate and 0.5g methylparaben were added to an appropriate amount of purified water and stirred to dissolve, forming a homogeneous solution containing bricetan.

[0062] 3) Slowly add the solution containing bricetra to the solution in step 1), and quickly stir to mix evenly;

[0063] 4) Add 2g of polyvinyl alcohol (PVA), stir quickly until the appropriate viscosity is reached, then add 6.6g of disodium hydrogen phosphate to adjust the pH to about 5.5, stir well to obtain a solution.

[0064] 5) Apply the solution obtained in step 4) onto a non-woven fabric that has been treated with hydrophobicity using a scraping process. After laminating it with release paper, dry it in a 60°C oven for 1-3 hours, adjust the moisture content to 3%-8%, cool it, cut it, and seal it to obtain the bricetan gel patch.

[0065] Comparative Example 2: Preparation of Bericertan Gel Patch with Sodium Polyacrylate as Adhesive

[0066] Following the method of Comparative Example 1, only the sodium polyacrylate NP-700 was replaced with sodium polyacrylate NP-800, while the rest of the steps remained unchanged.

[0067] The formulations of Comparative Examples 1 and 2 are shown in Table 2.

[0068] Table 2

[0069]

[0070] The following experimental examples demonstrate the beneficial effects of the present invention.

[0071] Experimental Example 1: Determination of the initial tack of gel plaster

[0072] 1. Experimental Methods

[0073] According to the Chinese Pharmacopoeia 2020 edition, Part IV, General Chapter 0952, Method I (Determination of Initial Tack), the initial tack was determined using the rolling ball ramp stop method. Three tablets each from Examples 1-4 and Comparative Examples 1-2 were placed at 18-25℃ and 40%-70% relative humidity for at least 2 hours. The surfaces of the inclined plate and stainless steel balls were wiped with a wiping material soaked in anhydrous ethanol, and then carefully dried with a clean, lint-free cloth. This process was repeated at least three times until the surfaces of the inclined plate and stainless steel balls were visually inspected and found to be clean. The protective layer was removed, and the balls were placed in the center of an inclined plate with a 15° angle, gel side up. The upper and lower 10cm of the inclined plate were covered with a 0.25mm thick polyester film, leaving a 5cm gel surface exposed in the middle. Steel balls of different diameters were rolled freely down the inclined plate. The initial tack was evaluated based on the ball number of the largest steel ball that the gel surface could adhere to. The test results are shown in Table 3.

[0074] Table 3

[0075] sample Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 1 16 26 30 34 15 18 2 17 27 29 35 15 19 3 16 27 28 34 16 19

[0076] The test results showed that the initial tack of samples 1-4 was good. The initial tack of the gel plaster prepared with different amounts of polymethacryloxyethyltrimethylammonium chloride was different. The initial tack increased with the increase of polymethacryloxyethyltrimethylammonium chloride. When comparing the initial tack of different gel matrix types under the same amount, the initial tack of the gel plaster prepared with polymethacryloxyethyltrimethylammonium chloride was better than that of the samples prepared with sodium polyacrylate (NP-700, NP-800) gel matrix.

[0077] Experimental Example 2: Determination of the Adhesion of Gel Patches

[0078] According to the fourth method (determination of adhesion) of General Chapter 0952 of the 2020 edition of the Chinese Pharmacopoeia, the adhesion was tested using a BLD-200N testing machine. Three gel patches from Examples 1-4 and Comparative Examples 1-2 were taken and placed at 18-25℃ and 40%-70% relative humidity for at least 2 hours. They were then cut into 50mm*70mm pieces, with the adhesive side facing up, placed on the sample loading module, aligned with the scale lines, and the covers on both sides were slightly torn off. The exposed adhesive sides were pressed down with pressure strips, and the covers were carefully removed. The sample was then placed naturally and centered on the base plate of the fixture, ensuring it adhered smoothly to the base plate. The pressure plate was pressed down horizontally, and the base plate and pressure plate were fixed with bolts on both sides to ensure the adhesive side of the sample on the rectangular strip was evenly taut. The sample was then placed on the instrument, and the forward speed of the pressure roller was set to 600mm / min, and the backward speed to 21mm / min for testing. The test results are shown in Table 4.

[0079] Table 4

[0080]

[0081] The adhesion test results all meet the adhesion standards for gel patches specified in the 2020 edition of the Chinese Pharmacopoeia, namely 1000-200mN. In Example 1, the amount of gel matrix used was small, and the adhesion was relatively low. Gel patches prepared with gel matrix in the range of 8g-15g all showed good adhesion. Under the same dosage of gel matrix, the polymethacryloyloxyethyltrimethylammonium chloride of this invention has better adhesion than sodium polyacrylate (NP-700, NP-800).

[0082] Experimental Example 3: Determination of the release rate of gel patch

[0083] Take one gel patch each from Examples 1-4 and Comparative Examples 1-2, remove the anti-adhesive layer, and stick it to the mesh plate with double-sided tape, gel side up. According to Method 1 of the fourth method of Dissolution and Release Determination in General Chapter 0931 of Part IV of the Chinese Pharmacopoeia 2020, using pH 4.5 phosphate buffer as the dissolution medium, take samples at 0, 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, and 2 h, and simultaneously replenish the same volume of release medium at the same temperature. Filter the sample release solution through a 0.45 μm microporous membrane and take the filtrate as the test sample solution. The cumulative release of bricetam was determined by HPLC. The chromatographic conditions were as follows: octadecylsilane-bonded silica gel (e.g., Ascentis Express 4.6 × 100 mm, 2.7 μm) was used as the stationary phase; 0.1% phosphoric acid aqueous solution was used as mobile phase A; acetonitrile was used as mobile phase B; the detection wavelength was 205 nm; the injection volume was 10 μl; the column temperature was 40 °C; the flow rate was 1.0 mL per minute; and the injection volume was 10 μl.

[0084] Perform gradient elution according to the table below.

[0085]

[0086] The dissolution amount and cumulative dissolution amount of each patch were calculated based on peak area using the external standard method. The results of the release test are shown in Table 5.

[0087] Table 5

[0088]

[0089] The experimental results above show that the samples obtained in Examples 1 to 4 of this invention have good dissolution and release rates, with a cumulative dissolution of more than 85% in 15 minutes, i.e., rapid dissolution. Dissolution equilibrium is reached after 1 hour, and the API is basically completely dissolved and released, ensuring the efficacy of the medication. In contrast, under the same gel matrix dosage in Formulas 1 to 2, the cumulative dissolution in 15 minutes is less than 85%, the cumulative dissolution at each time point in the first 45 minutes is relatively low, and the cumulative dissolution at the final dissolution plateau is relatively low, indicating slower release.

[0090] Based on the combined results of initial tack, adhesion, and release rate measurements, patches prepared using polymethacryloyloxyethyltrimethylammonium chloride as the gel matrix within the range of 3% to 15% basically meet the quality requirements of patches. The gel patch prepared with a dosage range of 8% to 12% exhibits the best quality and release effect. Compared with sodium polyacrylate (NP-700, NP-800), gel patches prepared with the same dosage of polymethacryloyloxyethyltrimethylammonium chloride as the gel matrix show better initial tack, adhesion, and release rate, resulting in better drug efficacy.

[0091] Experimental Example 4: Compatibility of the gel matrix of the present invention with briracetam

[0092] For topical semi-solid dosage forms, there are currently no guidelines regarding the compatibility of raw materials and excipients. Referring to the compatibility testing methods for raw materials and excipients in solid dosage forms, the compatibility of individual raw materials and combinations of single excipients and raw materials was examined. Specifically, bricetam and bricetam + polymethacryloyloxyethyltrimethylammonium chloride (1:1) were tested. The raw materials and excipients were weighed according to the ratio, mixed, and divided into four portions each. These portions were placed in dry, clean petri dishes. One portion was used as the day 0 sample, and the remaining three portions were placed under high temperature (60℃), high humidity (RH 75%), and light exposure (1.2 × 10⁻⁶) respectively. 6 lx·hr, illuminance approximately 4500 lx per hour, near-ultraviolet energy approximately 200 W·hr / m 2 Under the specified conditions, samples were taken at 5, 10, or 12 days to examine appearance and related substances. The test results are shown in Table 6.

[0093] Table 6

[0094]

[0095] Note: The chromatographic conditions for related substances are the same as those for the assay. The concentration of the test solution is 1 mg / ml, and the concentration of the reference standard (2-(2-oxo-4-tetrahydropropyl-1H-pyrrolo-1-yl)butyric acid, molecular weight 213.27, CAS: 943986-67-2) solution is 2 μg / ml. The impurity content is calculated by external standard method.

[0096] The experimental results above show that, under high temperature and high humidity conditions, neither API alone nor API + polymethacryloxyethyltrimethylammonium chloride exhibits significant changes in related substances. However, polymethacryloxyethyltrimethylammonium chloride is hygroscopic and shows clumping, altering its properties. Under light conditions, both introduce new unknown impurities, but these levels are below the reporting limit. The trends of both are consistent. As an excipient for gel patches, polymethacryloxyethyltrimethylammonium chloride does not exhibit clumping after absorbing moisture, indicating good compatibility between API and polymethacryloxyethyltrimethylammonium chloride.

[0097] In summary, this invention provides a novel dosage form of bricetramine: a gel patch. Using polymethacryloyloxyethyltrimethylammonium chloride as the key adhesive component in the gel patch, the prepared gel patch exhibits excellent adhesion, good compatibility with the active drug bricetramine, and good sustained-release behavior, showing broad application prospects.

Claims

1. The use of polymethacryloyloxyethyltrimethylammonium chloride as an adhesive for the paste layer of a gel patch, characterized in that: The gel patch has a paste layer made from an aqueous solution containing the following mass fractions of raw materials and excipients: The aqueous solution contains 0.1–10% wt of active drug, 3–15% wt of adhesive, 1–10% wt of transdermal penetration enhancer, and 4–15% wt of humectant; the pH of the aqueous solution is 5–6; the active drug is brucetan. The preparation method of the polymethacryloyloxyethyltrimethylammonium chloride is as follows: DMC monomer and initiator are dissolved in water, reacted at 30-40°C for 2-4 hours under inert gas protection, and then the temperature is raised to 45-55°C for 1-3 hours. The number-average molecular weight of the polymethacryloyloxyethyltrimethylammonium chloride is 4 × 10⁻⁶. 7 ~5×10 7 ; and / or the weight-average molecular weight of the polymethacryloyloxyethyltrimethylammonium chloride is 4 × 10⁻⁶. 7 ~5×10 7 ; and / or the Z-average relative molecular mass of the polymethacryloyloxyethyltrimethylammonium chloride is 5.5 × 10⁻⁶. 7 ~6×10 7 .

2. The use as described in claim 1, characterized in that, The gel patch has a paste layer made from an aqueous solution containing the following mass fractions of raw materials and excipients: Active drug 5% wt, adhesive 3-15% wt, transdermal penetration enhancer 3% wt, moisturizer 8% wt.

3. The use as described in claim 2, characterized in that, The gel patch has a paste layer made from an aqueous solution containing the following mass fractions of raw materials and excipients: Active drug 5% wt, adhesive 8-12% wt, transdermal penetration enhancer 3% wt, moisturizer 8% wt.

4. The use as described in claim 2, characterized in that, The transdermal penetration enhancer is one or more of the following: laurocapram, propylene glycol, eucalyptus oil, camphor, diisopropyl adipate, and 1-menthol. And / or the moisturizer is glycerin, polyethylene glycol, hyaluronic acid, panthenol, sorbitol or sodium alginate.

5. The use as described in claim 4, characterized in that, The transdermal penetration enhancer is a combination of laurocapram and propylene glycol; And / or the moisturizer is glycerin.

6. The use as described in claim 5, characterized in that, The mass ratio of laurocapram to propylene glycol is 2:

1.

7. The use as described in claim 2, characterized in that, The aqueous solution also contains stabilizers and preservatives, wherein the stabilizers are buffer pairs consisting of a conjugate acid and a conjugate base.

8. The use as described in claim 7, characterized in that, The stabilizer is a combination of sodium hydrogen phosphate and sodium dihydrogen phosphate, a combination of acetic acid and sodium acetate, a combination of citric acid and sodium citrate, or a combination of tartaric acid and sodium tartrate. The preservative is methylparaben, ethylparaben, benzyl alcohol, or benzoic acid.

9. The use as described in claim 8, characterized in that, The stabilizer is a combination of sodium hydrogen phosphate and sodium dihydrogen phosphate; The preservative is methylparaben.

10. The use as described in claim 7, characterized in that, The amount of stabilizer used is 5-10% wt, and the amount of preservative used is 0.1-0.6% wt.

11. The use as described in claim 10, characterized in that, The amount of stabilizer used is 7.9% wt, and the amount of preservative used is 0.5% wt.

12. The use as described in claim 2, characterized in that, The gel patch's paste layer is prepared from the following raw materials by mass fraction: The active pharmaceutical ingredient comprises 5% wt, adhesive 3-15% wt, transdermal penetration enhancer 3% wt, moisturizer 8% wt, stabilizer 7.9% wt, preservative 0.5% wt, and the balance being water.

13. The use as described in claim 12, characterized in that, The gel patch's paste layer is prepared from the following raw materials by mass fraction: The active pharmaceutical ingredient comprises 5% wt of active drug, 8-12% wt of adhesive, 3% wt of transdermal penetration enhancer, 8% wt of moisturizer, 7.9% wt of stabilizer, 0.5% wt of preservative, and the balance being water.

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