Low-irritation methyl salicylate gel patch and preparation method thereof

Abstract

The invention relates to a low-irritation methyl salicylate gel patch and a preparation method thereof, and belongs to the field of medical supplies. According to the gel patch, 5%-10% of methyl salicylate is taken as an active component, and is matched with a basic polymer, a cross-linking agent, a propylene glycol-free humectant, a soothing agent (containing bisabolol, tocopheryl acetate and aloe extract) and other components, and through the synergistic effect of all the components, the irritation is remarkably reduced while the analgesic effect of high-concentration methyl salicylate is ensured. The preparation method comprises the steps of pre-mixing oil-soluble components, preparing a water phase and an oil phase in a split-phase manner, stirring and mixing in vacuum, standing and curing and the like, and key parameter control ensures that a system is uniform and stable. The gel patch is free of sensitization and suitable for most people (including sensitive skin), the preparation process is simple and easy to popularize, and the problem that an existing high-concentration methyl salicylate patch is high in irritation is solved.

Description

Technical Field

[0001] This invention belongs to the field of medical supplies technology, specifically relating to the preparation technology of topical analgesic gel patches, and particularly to a low-irritant gel patch containing a high concentration of methyl salicylate and its preparation method. Background Technology

[0002] Methyl salicylate (also known as wintergreen oil) is a key active ingredient in topical analgesic gel patches. It promotes local blood circulation, has mild anti-inflammatory effects, and relieves muscle and joint pain and stiffness, making it widely used in the medical field. It exerts its therapeutic effect by altering the skin barrier structure, but it is inherently irritating to the skin, and this irritation increases significantly with increasing concentration—when the concentration exceeds 5%, the skin often experiences a strong burning sensation or discomfort, severely limiting the application of high-concentration methyl salicylate gel patches.

[0003] In existing technologies, reducing the irritation of salicylic acid compounds usually requires lowering their concentration, leading to weakened efficacy; or adjusting irritation through a single ingredient, with limited effectiveness. For example, Chinese patent CN202110424250.8 discloses a topical, low-irritant salicylic acid gel, which improves the solubility of salicylic acid in water and reduces its direct contact with the skin through the synergistic effect of cosolvents (such as propylene glycol and glycerin) and encapsulating agents (cyclodextrin and cellulose derivatives), thereby reducing irritation and making it suitable for anti-acne and keratolytic applications in the skincare field. However, this technology has the following limitations: Firstly, the active ingredient is salicylic acid, which has a fundamentally different chemical structure and pharmacological effects from methyl salicylate (salicylic acid is mainly used for keratin regulation, while methyl salicylate focuses on analgesia and anti-inflammation). Secondly, its low-irritation mechanism relies on the encapsulation of the active ingredient by the encapsulating agent, which may delay the release of the drug and allow the use of propylene glycol (which is known to damage the lipids of the stratum corneum and aggravate irritation). Third, it does not address the irritation caused by high concentrations (5%~10%) of methyl salicylate, and it cannot meet the dual requirements of rapid onset and low irritation for analgesic patches in the medical field.

[0004] Therefore, how to significantly reduce skin irritation by increasing the concentration of methyl salicylate to enhance the analgesic effect while using a novel mechanism different from encapsulation technology has become a pressing technical problem in this field. Summary of the Invention

[0005] The purpose of this invention is to address the problems in the prior art, such as the significantly increased skin irritation of methyl salicylate gel patches at concentrations exceeding 5%, making it difficult to balance high-concentration analgesic effects with low irritation, thus limiting its applicability. This invention provides a gel patch and its preparation method that utilizes a specific ratio of soothing agents (synergistic effects of bisabolol, tocopheryl acetate, and aloe extract) and other auxiliary ingredients (including moisturizers, polymers, etc., excluding propylene glycol), combined with phase separation preparation and vacuum stirring processes, to maintain low irritation of methyl salicylate at high concentrations of 5% to 10%.

[0006] To achieve the aforementioned objectives, in a first aspect, the present invention employs the following technical solution: a method for preparing a low-irritant methyl salicylate gel patch includes the following steps: A: Premix the bisabolol, aloe extract and isopropyl myristate in the soothing agent, and stir at 300-500 rpm for 10-15 minutes; B: Stir water, crosslinking regulator, polyvinylpyrrolidone (from the thickener), preservative, and Tween 80 at 800-1200 rpm for 10-20 minutes to form an aqueous phase; C: Stir the humectant, basic polymer, crosslinking agent, filler, sodium carboxymethyl cellulose (from the thickener), and tocopheryl acetate (from the soothing agent) at 800-1200 rpm for 20-25 min to form an oil phase; add the premix from step A and methyl salicylate to the oil phase and continue stirring for 5-10 min. D: Pour the aqueous phase from step B and the mixture from step C into a dual planetary vacuum mixer and stir to obtain a hydrogel; E: Coat the hydrogel, cut it into semi-finished products, and let it stand to obtain low-irritant methyl salicylate gel patches.

[0007] Furthermore, in step D, the stirring vacuum degree is -0.08MPa, the stirring frequency is 40~50Hz, and the stirring time is 6~10 minutes.

[0008] Furthermore, in step E, the settling temperature is 25~30℃ and the settling time is 16~24h.

[0009] Secondly, a low-irritant methyl salicylate gel patch prepared by the above-described preparation method is characterized by comprising the following components by weight percentage: The composition includes methyl salicylate 5%~10%, basic polymer 4%~7%, crosslinking agent 0.1%~0.25%, crosslinking regulator 0.15%~0.3%, humectant 10%~30%, thickener 0.5%~5%, isopropyl myristate 0.5%~5%, Tween 80 0.05%~5%, preservative 0.2%~0.8%, soothing agent 0.1%~5%, filler 0.1%~0.5%, and the balance being water; the humectant is a polyol without propylene glycol.

[0010] Furthermore, the moisturizer is one or more of glycerin, sorbitol, butylene glycol, and diethylene glycol.

[0011] Furthermore, the basic polymer is partially neutralized polyacrylic acid with a neutralization degree of 35% to 65%.

[0012] Furthermore, the crosslinking agent is Ca 2+ Al 3+ Mg 2+ It is a salt of an ion, selected from one or more of aluminum hydroxide, aluminum hydroxyl, aluminum chloride, calcium oxide, and magnesium carbonate.

[0013] Furthermore, the crosslinking regulator is one or more of citric acid, tartaric acid, lactic acid, malic acid, and ethylenediaminetetraacetic acid.

[0014] Furthermore, the thickener is one or more of methylcellulose, croscarmellose sodium, polyvinylpyrrolidone, carbomer, sodium carboxymethylcellulose, sodium alginate, and polyvinyl alcohol.

[0015] Furthermore, the preservative is one or more of methylparaben, ethylparaben, and DMDM ​​hydantoin.

[0016] Furthermore, the filler is one or more of kaolin, titanium dioxide, expansive soil, and zinc oxide.

[0017] Furthermore, the soothing agents include one or more of bisabolol, tocopheryl acetate, and aloe extract.

[0018] Compared with the prior art, the present invention has the following beneficial effects: 1. Significantly reduced irritation: By synergistically blocking the activation of pain receptors and inhibiting inflammatory pathways through three soothing agents, combined with the elimination of irritating components (such as propylene glycol), low irritation can still be achieved at a methyl salicylate concentration of 5%~10%, thus resolving the contradiction between high concentration and high irritation; 2. Guaranteed efficacy: High-concentration methyl salicylate can fully exert its analgesic and anti-inflammatory effects, and its efficacy is superior to that of low-concentration products; 3. Wide range of applications: Gentle on the skin, non-allergenic, and suitable for most people, including those with sensitive skin; 4. Stable and controllable process: The preparation method is simple, and the uniformity of the system is ensured by steps such as phase separation stirring and vacuum mixing, which makes it easy to industrialize and promote. Attached Figure Description

[0019] Figure 1 This is a flowchart of the preparation method of the present invention. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention are within the scope of protection of the present invention.

[0021] Those skilled in the art should understand that, in the disclosure of this invention, the terms "longitudinal," "lateral," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, the above terms should not be construed as limiting this invention.

[0022] Example 1 refer to Figure 1 The preparation method of this low-irritant methyl salicylate gel patch includes the following steps (by weight): A: Mix 0.2% bisabolol, 2% isopropyl myristate, and 1% aloe extract at 500 rpm for 15 min to obtain phase A.

[0023] B: Then add 50.55% water, 0.25% tartaric acid, 3% PVP-k90, 0.3% DMDM ​​hydantoin, and 0.05% Tween 80 to the tank. Stir at 1000 rpm for 20 minutes to obtain phase B.

[0024] C: In another container, add 24% glycerol, 5.2% sodium polyacrylate (neutralization degree 40%), 0.15% aluminum hydroxyl, 0.3% kaolin, 1% sodium carboxymethyl cellulose, and 2% tocopheryl acetate. Stir at 1000 rpm for 20 minutes. Then add phase A and 10% methyl salicylate in sequence and continue stirring for 5 minutes to obtain phase C.

[0025] D: Then, phase B and phase C were added sequentially to the dual planetary vacuum stirrer and stirred. The vacuum degree was -0.08MPa, the stirring rate was 45Hz, and the stirring time was 8min.

[0026] E: The obtained colloid is coated and cut on a coating machine to obtain a semi-finished patch. Finally, it is left to stand at 25°C for 20 hours to obtain the finished product - low-irritant methyl salicylate gel patch.

[0027] The methyl salicylate gel patch from Example 1 was provided to fifty volunteers for trial use. None of them reported any allergic reactions. Regarding feedback on irritation, 47 people reported mild irritation and 3 people reported no irritation.

[0028] Example 2 Based on the same concept, the preparation method of this low-irritant methyl salicylate gel patch includes the following steps (by weight): A: Mix 0.4% bisabolol, 0.5% isopropyl myristate, and 2% aloe extract at 400 rpm for 12 min to obtain phase A.

[0029] B: Then add 53.03% water, 0.20% citric acid, 2% PVP-K90, 0.25% methylparaben, and 0.1% Tween 80 to the bucket, and stir at 1200 rpm for 18 minutes to obtain phase B.

[0030] C: In another container, add 18% glycerol, 6% sorbitol, 4.8% sodium polyacrylate (neutralization degree 45%), 0.12% aluminum hydroxide, 0.1% titanium dioxide, 1.5% sodium carboxymethyl cellulose, and 3% tocopheryl acetate. Stir at 1100 rpm for 21 min. Then add phase A and 8% methyl salicylate in sequence and continue stirring for 7 min to obtain phase C.

[0031] D: Then, phase B and phase C were added sequentially to the dual planetary vacuum stirrer and stirred. The vacuum degree was -0.08MPa, the stirring rate was 40Hz, and the stirring time was 10min.

[0032] E: The obtained colloid is coated and cut on a coating machine to obtain a semi-finished patch. Finally, it is left to stand at 26°C for 18 hours to obtain the finished product—a low-irritant methyl salicylate gel patch.

[0033] The methyl salicylate gel patch from Example 2 was provided to fifty volunteers for trial use. No allergic reactions were reported. Regarding irritation, 46 volunteers reported mild irritation and 4 volunteers reported no irritation.

[0034] Example 3 Based on the same concept, the preparation method of this low-irritant methyl salicylate gel patch includes the following steps (by weight): A: Mix 0.5% bisabolol, 3% isopropyl myristate, and 3% aloe extract at 350 rpm for 13 min to obtain phase A.

[0035] B: Then add 57.85% water, 0.15% citric acid, 2.5% PVP-k90, 0.2% DMDM ​​hydantoin, and 0.5% Tween 80 to the bucket. Stir at 1000 rpm for 20 minutes to obtain phase B.

[0036] C: In another container, add 15% glycerol, 5% butanediol, 5% sodium polyacrylate (neutralization degree 45%), 0.2% aluminum hydroxyl, 0.3% expanded clay, 0.8% sodium carboxymethyl cellulose, and 1% tocopheryl acetate. Stir at 1000 rpm for 22 minutes. Then add phase A and 5% methyl salicylate in sequence and continue stirring for 5 minutes to obtain phase C.

[0037] D: Then, phase B and phase C were added sequentially to the dual planetary vacuum stirrer and stirred. The vacuum degree was -0.08MPa, the stirring rate was 50Hz, and the stirring time was 7min.

[0038] E: The obtained colloid is coated and cut on a coating machine to obtain a semi-finished patch. Finally, it is left to stand at 28°C for 19 hours to obtain the finished product—a low-irritant methyl salicylate gel patch.

[0039] The methyl salicylate gel patch of Example 3 was provided to fifty volunteers for trial use. No allergic reactions were reported. Regarding irritation, 48 people reported mild irritation and 2 people reported no irritation.

[0040] Example 4 Based on the same concept, the preparation method of this low-irritant methyl salicylate gel patch includes the following steps (by weight): A: Mix 1% bisabolol, 5% isopropyl myristate, and 4% aloe extract at 300 rpm for 15 min to obtain phase A.

[0041] B: Then add 57.92% water, 0.23% tartaric acid, 0.1% ethylenediaminetetraacetic acid, 1.8% PVP-k90, 0.5% ethyl p-hydroxybenzoate, and 2% Tween 80 to the tank. Stir at 1100 rpm for 15 minutes to obtain phase B.

[0042] C: In another container, add 10% glycerol, 8% sorbitol, 7% sodium polyacrylate (neutralization degree 50%), 0.15% magnesium hydroxide, 0.1% zinc oxide, 1.2% sodium alginate, and 3% tocopheryl acetate. Stir at 1200 rpm for 21 min. Then add phase A and 6.2% methyl salicylate in sequence and continue stirring for 10 min to obtain phase C.

[0043] D: Then, phase B and phase C were added sequentially to the dual planetary vacuum stirrer and stirred. The vacuum degree was -0.08MPa, the stirring rate was 43Hz, and the stirring time was 9min.

[0044] E: The obtained colloid is coated and cut on a coating machine to obtain a semi-finished patch. Finally, it is left to stand at 27°C for 20 hours to obtain the finished product—a low-irritant methyl salicylate gel patch.

[0045] The methyl salicylate gel patch of Example 4 was provided to fifty volunteers for trial use. No allergic reactions were reported. For the irritation feedback, it was indicated that it was mildly irritating to 50 people.

[0046] Example 5 Based on the same concept, the preparation method of this low-irritant methyl salicylate gel patch includes the following steps (by weight): A: Mix 1.5% bisabolol, 4% isopropyl myristate, and 2.5% aloe extract at 400 rpm for 12 min to obtain phase A.

[0047] B: Then add 45.17% water, 0.25% malic acid, 2.5% PVP-k90, 0.2% DMDM ​​hydantoin, and 1.5% Tween 80 to the bucket. Stir at 900 rpm for 20 minutes to obtain phase B.

[0048] C: In another container, add 25% glycerol, 6% sodium polyacrylate (neutralization degree 45%), 0.23% calcium hydroxide, 0.35% kaolin, 0.8% sodium alginate, and 2.5% tocopheryl acetate. Stir at 800 rpm for 25 minutes. Then add phase A and 7.5% methyl salicylate in sequence and continue stirring for 9 minutes to obtain phase C.

[0049] D: Then, phase B and phase C were added sequentially to the dual planetary vacuum stirrer and stirred. The vacuum degree was -0.08MPa, the stirring rate was 50Hz, and the stirring time was 10min.

[0050] E: The obtained colloid is coated and cut on a coating machine to obtain a semi-finished patch. Finally, it is left to stand at 30°C for 16 hours to obtain the finished product—a low-irritant methyl salicylate gel patch.

[0051] The methyl salicylate gel patch of Example 5 was provided to fifty volunteers for trial use. No allergic reactions were reported. Regarding irritation, 45 people reported mild irritation and 5 people reported no irritation.

[0052] Example 6 Based on the same concept, the preparation method of this low-irritant methyl salicylate gel patch includes the following steps (by weight): A: Mix 0.1% bisabolol, 5% isopropyl myristate, and 5% aloe extract at 300 rpm for 15 min to obtain phase A.

[0053] B: Then add 50.7% water, 0.3% lactic acid, 5% PVP-K90, 0.8% ethylparaben, and 5% Tween 80 to the bucket. Stir at 800 rpm for 20 minutes to obtain phase B.

[0054] C: In another container, add 10% glycerol, 4% sodium polyacrylate (neutralization degree 40%), 0.1% calcium carbonate, 0.5% kaolin, 0.5% sodium carboxymethyl cellulose, and 4% tocopheryl acetate. Stir at 900 rpm for 25 minutes. Then add phase A and 9% methyl salicylate in sequence and continue stirring for 10 minutes to obtain phase C.

[0055] D: Then, phase B and phase C were added sequentially to the dual planetary vacuum stirrer and stirred. The vacuum degree was -0.08MPa, the stirring rate was 40Hz, and the stirring time was 6min.

[0056] E: The obtained colloid is coated and cut on a coating machine to obtain a semi-finished patch. Finally, it is left to stand at 25°C for 24 hours to obtain the finished product—a low-irritant methyl salicylate gel patch.

[0057] The methyl salicylate gel patch of Example 6 was provided to fifty volunteers for trial use. No allergic reactions were reported. Regarding irritation, 43 volunteers reported mild irritation and 7 volunteers reported no irritation.

[0058] Comparative Example 1 The implementation method is the same as in Example 1, except that: The composition of the salicylate gel patch was 0.01% bisabolol, 0.01% tocopheryl acetate, 0.01% aloe vera extract, and 53.72% water. The final product was a methyl salicylate gel patch. The gel patch from Comparative Example 1 was provided to fifty volunteers for trial use. No allergic reactions were reported. Regarding irritation, all fifty volunteers reported a strong irritation.

[0059] Comparing Comparative Example 1 and Example 1, it can be seen that under the same testing conditions, adding very little or no soothing agent directly leads to a strong irritation of the skin. This is because the gel patch contains little or no soothing agent, which cannot effectively block the activation of TRPV1 pain receptors, resulting in the methyl salicylate gel patch being more irritating and causing a strong burning sensation.

[0060] Comparative Example 2 The implementation method is the same as in Example 1, except that: Without adding bisabolol, and with a water content of 50.75%, methyl salicylate gel patches were finally prepared. The gel patches from Comparative Example 2 were provided to fifty volunteers for trial use. None experienced allergic reactions. Regarding feedback on irritation, 47 volunteers reported mild irritation, 2 reported strong irritation, and 1 reported no irritation.

[0061] Comparing Comparative Example 2 and Example 1, it can be seen that under the same test conditions, the absence of bisabolol increases the irritation of methyl salicylate gel patch. This is because bisabolol can effectively block the activation of TRPV1 pain receptors and effectively inhibit the COX-2 inflammatory pathway, thus having anti-inflammatory and burning-reducing effects.

[0062] Comparative Example 3 The implementation method is the same as in Example 1, except that: Without the addition of tocopheryl acetate and with a water content of 52.55%, methyl salicylate gel patches were finally prepared. The gel patches from Comparative Example 3 were provided to fifty volunteers for trial use; none experienced allergic reactions. Regarding feedback on irritation, 48 volunteers reported mild irritation, and 2 reported strong irritation.

[0063] Comparing Comparative Example 3 and Example 1, it can be seen that under the same test conditions, tocopherol acetate can reduce the irritation of methyl salicylate gel patch. This is because tocopherol acetate can effectively block the activation of TRPV1 pain receptors and has antioxidant and de-irritant effects.

[0064] To verify the effectiveness of this invention, 40 pieces of back skin from freshly slaughtered healthy domestic pigs (Large White pigs) were selected and divided into three groups: a blank group (blank patch without methyl salicylate), a positive control group (5% sodium lauryl sulfate solution), and a gel patch group (the product from Example 1 was used in this group). The pig skin was carefully peeled off, subcutaneous fat tissue was removed, and the skin was cleaned with physiological saline to prepare skin patches for later use. The blank patch, 5% sodium lauryl sulfate solution, and gel patch group were applied or applied to the prepared pig skin. After 6 hours, the drugs were removed with warm water, and the skin allergic reaction was observed. Finally, the skin was observed again at 12h, 18h, and 24h.

[0065] Experimental Results: In the blank patch group, allergic reactions were zero at 6h, 12h, 18h, and 24h, and skin irritation was assessed as non-irritating. In the positive control group, the allergic reaction rate was 100% at 6h, 80% at 12h, 40% at 18h, and 0% at 24h, and skin irritation was assessed as significantly irritating. In the gel patch group, allergic reactions were zero at 6h, 12h, 18h, and 24h, and skin irritation was assessed as low-irritating. Table 1 below shows the symptom scores of the hydrogel patch skin irritation test on pigskin: Table 1

[0066] Where: "0" indicates no erythema; "1" indicates mild erythema; "2" indicates significant erythema.

[0067] Table 1 shows that the gel patch of the present invention is non-sensitizing and only has extremely low irritation (mild erythema in a few samples) compared with the blank group (no irritation) and the positive control group (5% sodium lauryl sulfate, significant irritation). This demonstrates that the present invention achieves low irritation of a high-concentration methyl salicylate gel patch through the synergistic design of "formulation-process-effect," making it suitable for most people (including sensitive skin), and its preparation is simple and easy to promote.

[0068] To demonstrate that propylene glycol does indeed disrupt the barrier and lead to enhanced stimulation, the present invention also conducted the following tests: Step 1: After washing their arms in advance, the 10 volunteers sat quietly for 30 minutes in a windless environment at 20-22℃ and 40-60% RH to acclimatize to the environment.

[0069] Step 2: Select 10cm sections on each of the left and right arms of each volunteer. 2 The selected area was chosen as the test area. Hair was removed from this area, and the area was marked with a marker. The initial TEWL value of the selected area of ​​the arm was measured using the Tewameter® open transdermal moisture loss probe and recorded as the T0 baseline value.

[0070] Step 3: Replace methyl salicylate in Comparative Example 1 with 10% propylene glycol, and designate this as the experimental group. Replace methyl salicylate in Comparative Example 1 with 10% water, and designate this as the control group. Apply the experimental group to the right arm area and the control group to the left arm area, and leave them on for 6 hours under the same conditions.

[0071] Step 4: After the specified time has elapsed, gently peel off the gel patch at 180°C and immediately test the TEWL value at this moment, and record the data at this time as T1.

[0072] Step 5: After removing the gel patch, record the TEWL values ​​at specified times 30 min, 1 h, and 2 h after removal, and denot them as T2, T3, and T4, respectively.

[0073] Step 6: As can be seen, the transepidermal water loss (TEWL) value of the experimental group with 10% propylene glycol added was significantly higher than that at T0 after the patch was removed, indicating that propylene glycol has a certain degree of skin irritation. See Table 2 below for specific data: Table 2 TEWL values ​​of each test group at different time points (unit: g·m) -2 ·h -1 (n=10)

[0074] ▲ indicates a significant difference compared to its baseline T0 value; * There were significant differences compared to the control group at the same time point.

[0075] To demonstrate the unexpected effects of the compositions of the present invention, the IC50 values ​​of each active ingredient, individually and in combination, against the human TRPV1 receptor were also evaluated using a fluorescence calcium flux assay. The three soothing agents in Example 1 were added individually, and the other two were replaced with water. The case with bisabolol added alone was designated as Example 1a, the case with tocopheryl acetate added alone was designated as Example 1b, and the case with aloe extract added alone was designated as Example 1c.

[0076] The experimental results showed that Experimental Examples 1a and 1c exhibited certain TRPV1 inhibitory activity, with IC50 values ​​of 46.7 μM and 65.4 μM, respectively. Experimental Example 1b showed weaker activity, with an IC50 value greater than 100 μM, while Experimental Example 1 showed significantly lower activity than any single component, with an IC50 value of 17.2 μM, indicating that the three components had a synergistic effect.

[0077] The parts of this invention not described in detail are prior art, therefore they are not described in detail here.

[0078] It is understood that the term "a" should be understood as "at least one" or "one or more", that is, in one embodiment, the number of an element can be one, while in another embodiment, the number of the element can be multiple, and the term "a" should not be understood as a limitation on the number.

[0079] Although this document uses a considerable amount of technical terminology, the possibility of using other terms is not excluded. These terms are used merely for the convenience of describing and explaining the essence of the invention; interpreting them as any additional limitation would contradict the spirit of the invention.

[0080] This invention is not limited to the preferred embodiments described above. Anyone can derive other products in various forms under the guidance of this invention. However, regardless of any changes made to their shape or structure, any technical solution that is the same as or similar to this invention falls within the protection scope of this invention.

Claims

1. A method for preparing a low-irritation methyl salicylate gel patch, characterized in that, Includes the following steps: A: Premix the bisabolol, aloe extract and isopropyl myristate in the soothing agent, and stir at 300-500 rpm for 10-15 minutes; B: Stir water, crosslinking regulator, polyvinylpyrrolidone (from the thickener), preservative, and Tween 80 at 800-1200 rpm for 10-20 minutes to form an aqueous phase; C: Stir the humectant, basic polymer, crosslinking agent, filler, sodium carboxymethyl cellulose (from the thickener), and tocopheryl acetate (from the soothing agent) at 800-1200 rpm for 20-25 min to form an oil phase; add the premix from step A and methyl salicylate to the oil phase and continue stirring for 5-10 min. D: Pour the aqueous phase from step B and the mixture from step C into a dual planetary vacuum mixer and stir to obtain a hydrogel; E: Coat the hydrogel, cut it into semi-finished products, and let it stand to obtain low-irritant methyl salicylate gel patches.

2. The preparation method according to claim 1, characterized in that, In step D, the stirring vacuum degree is -0.08MPa, the stirring frequency is 40~50Hz, and the stirring time is 6~10 minutes.

3. The preparation method according to claim 1, characterized in that, In step E, the settling temperature is 25~30℃ and the settling time is 16~24h.

4. A low-irritation methyl salicylate gel patch prepared by the preparation method according to any one of claims 1-3, characterized in that, Includes the following ingredients by weight percentage: The composition includes methyl salicylate 5%~10%, basic polymer 4%~7%, crosslinking agent 0.1%~0.25%, crosslinking regulator 0.15%~0.3%, humectant 10%~30%, thickener 0.5%~5%, isopropyl myristate 0.5%~5%, Tween 80 0.05%~5%, preservative 0.2%~0.8%, soothing agent 0.1%~5%, filler 0.1%~0.5%, and the balance being water; the humectant is a polyol that does not contain propylene glycol.

5. The low-irritation methyl salicylate gel patch according to claim 4, characterized in that, The moisturizer is one or more of glycerin, sorbitol, butylene glycol, and diethylene glycol.

6. The low-irritation methyl salicylate gel patch according to claim 4, characterized in that, The basic polymer is partially neutralized polyacrylic acid with a neutralization degree of 35% to 65%.

7. The low-irritation methyl salicylate gel patch according to claim 4, characterized in that, The crosslinking agent is Ca 2 + Al 3+ Mg 2+ It is a salt of ions, selected from one or more of aluminum hydroxide, aluminum hydroxyl, aluminum chloride, calcium oxide, and magnesium carbonate.

8. The low-irritation methyl salicylate gel patch according to claim 4, characterized in that, The crosslinking regulator is one or more of citric acid, tartaric acid, lactic acid, malic acid, and ethylenediaminetetraacetic acid.

9. The low-irritation methyl salicylate gel patch according to claim 4, characterized in that, The thickener is one or more of methylcellulose, croscarmellose sodium, polyvinylpyrrolidone, carbomer, sodium carboxymethylcellulose, sodium alginate, and polyvinyl alcohol.

10. The low-irritation methyl salicylate gel patch according to claim 4, characterized in that, The preservative is one or more of methylparaben, ethylparaben, and DMDM ​​hydantoin; The filler is one or more of kaolin, titanium dioxide, expansive soil, and zinc oxide; The soothing agent includes one or more of bisabolol, tocopheryl acetate, and aloe extract.

Images