External traditional Chinese medicine patch for relieving abdominal pain of children and preparation method of external traditional Chinese medicine patch

Abstract

The invention discloses a traditional Chinese medicine external preparation technology, and belongs to an external traditional Chinese medicine patch for relieving abdominal pain of children and a preparation method of the external traditional Chinese medicine patch. The problems that an existing traditional Chinese medicine patch is insufficient in medicine compatibility pertinence, low in transdermal absorption efficiency, slow in effect taking, insufficient in safety and the like are solved. The patch is suitable for children of all ages, can comprehensively cope with stomachache caused by various causes of diseases, has the characteristics of quick response, high safety and good comfort, and remarkably improves the clinical curative effect and social benefit.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine external preparations, and particularly relates to an external traditional Chinese medicine patch for relieving children's abdominal pain and a preparation method thereof. Background Art

[0002] In pediatric clinical treatment, children's abdominal pain is a common disease, and its causes are complex and diverse, including cold-damp blockage, qi stagnation and blood stasis, spleen and stomach weakness, etc. Although existing traditional Chinese medicine patches can relieve symptoms to a certain extent, there are generally problems such as insufficient pertinence of drug compatibility, low transdermal absorption efficiency, and slow onset of action.

[0003] Current pediatric external patches have multi-dimensional limitations in clinical application: First, the accuracy of syndrome differentiation and treatment is insufficient. Existing products mostly focus on single syndromes such as cold-damp blockage or spleen and stomach weakness (such as Dinggui'er umbilical patch, Shufu patch plaster), and there is a lack of systematic regulation schemes for complex pathological mechanisms such as qi stagnation and blood stasis, and damp-heat stasis. Second, there are structural defects in the formula compatibility. Traditional formulas overly rely on warming drugs such as cloves and cinnamon, and the compatibility ratios of qi-regulating drugs (costus root, green tangerine peel), blood-activating drugs (chuanxiong rhizome, peach kernel), and heat-clearing drugs (coptis root, scutellaria root) are unbalanced, making it difficult to meet the comprehensive conditioning needs of the syndrome of intermingled cold and heat. Third, the preparation process lags behind the development of modern pharmacy. Most products still use traditional matrices such as rubber plasters and hot-melt adhesives, lacking advanced technologies such as multi-layer barrier controlled release systems and microsphere carriers, resulting in easy migration and degradation of drugs during storage. Fourth, the transdermal absorption efficiency is limited. New transdermal technologies such as microneedle arrays and nanoemulsions are not fully applied, and the percutaneous penetration rate of drugs is generally lower than 15%. Fifth, the safety risks cannot be ignored. Some products contain easily sensitizing ingredients such as camphor and menthol (such as Shufu patch plaster), and traditional adhesives such as rubber plasters have insufficient air permeability. Clinical data show that the incidence of contact dermatitis in infants and young children after use is as high as 8.7%. These technical bottlenecks restrict the further popularization and application of external patches in the pediatric field. Summary of the Invention

[0004] In view of the above situation, to overcome the defects of the existing technology, the present invention improves the efficacy of traditional Chinese medicine patches by optimizing compatibility and combining high-efficiency transdermal technology. Based on the mechanisms of warming the meridians and dispelling cold, promoting qi and activating blood circulation, preferred synergistic traditional Chinese medicine components are selected for children's abdominal pain caused by etiologies such as cold-damp blockage. The nanoemulsification technology and penetration enhancers are used to improve the transdermal absorption efficiency, achieving rapid onset and long-lasting drug efficacy. Natural moisturizing factors and anti-irritant ingredients are added to the formula to enhance safety and comfort.

[0005] To achieve the above object, the following technical solution is adopted: An external traditional Chinese medicine patch for relieving children's abdominal pain and a preparation method thereof, including the following steps:

[0006] Step 1: Dissolve Artemisia argyi leaf extract (10 - 20 parts), Ligusticum chuanxiong volatile oil (5 - 15 parts), Eugenol (3 - 8 parts), Angelica dahurica powder (6 - 12 parts), Menthol (2 - 6 parts) and Glycyrrhiza glabra extract (4 - 10 parts) in anhydrous ethanol according to the weight ratio, and stir evenly;

[0007] Step 2: Add sodium polyoxyethylene ether sulfosuccinate (20 - 30 parts), a nano-emulsifying matrix, and ultrasonically emulsify for 30 minutes;

[0008] Step 3: Add 8 parts of penetration enhancer Azone, natural moisturizing factors Urea and Sodium Hyaluronate (2:1), and continue to stir for 1 hour to obtain a uniform ointment;

[0009] Step 4: Uniformly coat the prepared ointment on medical non-woven fabric, control the thickness between 0.5 - 1 mm, cover with release paper after drying, and cut into patch specifications;

[0010] Furthermore, the Artemisia argyi leaf extract in Step 1 has the effects of warming the meridians and dispelling cold, and relieving pain. Its main active ingredients are volatile oil and flavonoid compounds, which can relieve abdominal pain caused by cold-dampness by regulating local blood circulation. The Artemisia argyi leaf extract used in the embodiment of the present invention is from Jiangxi Baicaotang Pharmaceutical Co., Ltd. (Product number: BC20220315).

[0011] Furthermore, the Ligusticum chuanxiong volatile oil in Step 1 has the effects of promoting blood circulation to remove blood stasis and regulating qi to relieve pain. Its main components are ligustilide and tetramethylpyrazine. Research shows that Ligusticum chuanxiong volatile oil can relieve abdominal pain by inhibiting the production of prostaglandin E2 and reducing smooth muscle spasm.

[0012] Furthermore, the Angelica dahurica powder in Step 1 has the effects of expelling wind and cold, and detumescence and relieving pain. Its main active ingredients are coumarin compounds. These ingredients can relieve abdominal pain caused by cold-dampness blockage by dilating blood vessels and improving local microcirculation.

[0013] Furthermore, the Menthol in Step 1 is a natural monoterpenoid alcohol, which has the effects of cooling and analgesia and anti-inflammation. Its mechanism of action is to activate the transient receptor potential channel M8 (TRPM8) to produce a local cooling effect, thereby relieving pain.

[0014] Furthermore, the Glycyrrhiza glabra extract in Step 1 has the effects of coordinating the actions of various drugs, anti-inflammation and protecting gastric mucosa. Its main active ingredients are glycyrrhizic acid and glycyrrhetinic acid. These ingredients can enhance the overall efficacy by inhibiting the NF-KB signaling pathway and reducing the release of inflammatory factors.

[0015] Further, the nanoemulsion technology in the second step can refine drug particles to the nanometer level, significantly improving the transdermal absorption efficiency of drugs. The nanoemulsion matrix of the present invention is a new nanoemulsifier, sodium polyoxyethylene ether sulfosuccinate, prepared by reacting cetyl polyoxyethylene ether, succinic anhydride, triethylamine, and 4-dimethylaminopyridine (molar ratio 1:1.2:0.05) in 8V dichloromethane at 30 °C for 8 hours to obtain Compound 2. Compound 2 reacts with sulfur chloride (molar ratio 1:1.2) in 8V dichloromethane at room temperature for 8 hours, and then sodium hydroxide with a molar ratio of 1 is added to form a salt to generate the sodium sulfonate salt, and finally recrystallized with 5V ethanol at 80 °C to obtain sodium polyoxyethylene ether sulfosuccinate.

[0016] Further, in the third step, laurocapram is a commonly used penetration enhancer that can temporarily change the stratum corneum structure, enhance the diffusion rate of drug molecules, and thus improve the transdermal absorption efficiency of drugs.

[0017] Further, in the third step, natural moisturizing factors can keep the skin moist, reduce the irritation of the patch to children's skin, and improve the comfort of use. The natural moisturizing factors used in the embodiments of the present invention are a mixture of urea and sodium hyaluronate in a mass ratio of 2:1.

[0018] Further, the traditional Chinese medicine patch is applied to the umbilicus of children, applied for 4 - 6 hours each time, once a day, and used continuously for 3 days. During the application process, the drug is rapidly released through transdermal absorption to relieve abdominal pain symptoms.

[0019] Further, the application time can be appropriately adjusted according to the age and skin tolerance of children. It is recommended that the application time for infants is 2 - 4 hours, and for preschool children is 4 - 6 hours.

[0020] The beneficial effects of the present invention are as follows: Through precise drug compatibility design, it comprehensively covers various causes of childhood abdominal pain; by combining nanoemulsion technology with highly efficient penetration enhancers, it significantly improves the transdermal absorption efficiency and onset speed of drugs; relying on multi-target synergistic effects and rapid release mechanisms, it ensures that the drug efficacy is quickly exerted to relieve pain; at the same time, adding natural moisturizing factors and anti-irritant ingredients enhances the safety and comfort of use of the patch; in addition, optimizing the formula and preparation process makes the patch suitable for pediatric patients of different ages. These innovative measures not only improve the treatment effect but also expand the applicable population, providing a safer and more efficient treatment option for childhood abdominal pain. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 For sodium polyoxyethylene ether sulfosuccinate of the present invention;

[0022] Figure 2 For the synthesis route of sodium polyoxyethylene ether sulfosuccinate of the present invention;

[0023] The accompanying drawings are used to provide a further understanding of the present invention and form a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation to the present invention. Detailed implementation manners

[0024] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0025] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the present invention. The preferred implementation methods and materials described herein are only for illustrative purposes and do not limit the content of this application.

[0026] The experimental methods in the following embodiments are all conventional methods unless otherwise specified. The test materials used in the following embodiments are all obtained from commercial channels unless otherwise specified.

[0027] Example 1

[0028] An external traditional Chinese medicine patch for relieving children's abdominal pain and its preparation method

[0029] As Figure 1 and Figure 2 shown, the preparation method of the external traditional Chinese medicine patch is as follows:

[0030] Step 1: Dissolve 15 parts of artemisia argyi extract, 10 parts of ligusticum chuanxiong volatile oil, 5 parts of eugenol, 9 parts of angelica dahurica powder, 4 parts of menthol, and 7 parts of licorice extract by weight in anhydrous ethanol and stir evenly.

[0031] Step 2: Add 25 parts of nano-emulsifying matrix sodium polyoxyethylene ether sulfosuccinate and ultrasonic for 30 min. Sodium polyoxyethylene ether sulfosuccinate is bonded by cetyl polyoxyethylene ether and succinic anhydride. The conditions are that cetyl polyoxyethylene ether, succinic anhydride, triethylamine, and 4-dimethylaminopyridine (molar ratio of 1:1.2:0.05) react in dichloromethane (volume ratio of cetyl polyoxyethylene ether 1 g:8 mL) at 30 °C for 8 hours to prepare compound 2. Compound 2 reacts with sulfur chloride (molar ratio of 1:1.2) at room temperature in dichloromethane (volume ratio of compound 2 1 g:8 mL) for 8 hours, and then sodium hydroxide with a molar ratio of 1 is added in a molar ratio of 1 to form a sulfonate salt. Then, it is recrystallized with ethanol (volume ratio of compound 2 1 g:5 mL) at 80 °C to obtain sodium polyoxyethylene ether sulfosuccinate.

[0032] Step 3: Add 2 parts of penetration enhancer azone and 8 parts of natural moisturizing factors urea and sodium hyaluronate (2:1), and continue stirring for 1 hour to obtain a uniform ointment.

[0033] Step 4: Uniformly coat the prepared ointment on a medical non-woven fabric, control the thickness between 0.5 - 1 mm, then place it in a dry environment. After drying, cover it with release paper and cut it into circular patches with a diameter of 5 cm.

[0034] Example 2

[0035] An external Chinese medicine patch for relieving children's abdominal pain and its preparation method

[0036] The preparation method is as follows:

[0037] Step 1: Dissolve 10 parts of folium artemisiae argyi extract, 5 parts of volatile oil of ligusticum wallichii, 3 parts of eugenol, 6 parts of angelica dahurica powder, 2 parts of menthol, and 4 parts of glycyrrhiza glabra extract by weight in absolute ethanol and stir evenly.

[0038] Step 2: Add 20 parts of nano-emulsifying matrix sodium polyoxyethylene ether sulfosuccinate and sonicate for 30 min. Prepare sodium polyoxyethylene ether sulfosuccinate in the same way as in Step 2 of Example 1.

[0039] Step 3: Add 1 part of penetration enhancer azone and 6 parts of natural moisturizing factors urea and sodium hyaluronate (2:1), and continue stirring for 1 hour to obtain a uniform ointment.

[0040] Step 4: Uniformly coat the prepared ointment on a medical non-woven fabric, control the thickness between 0.5 - 1 mm, then place it in a dry environment. After drying, cover it with release paper and cut it into circular patches with a diameter of 5 cm.

[0041] Example 3

[0042] An external Chinese medicine patch for relieving children's abdominal pain and its preparation method

[0043] The preparation method is as follows:

[0044] Step 1: Dissolve 20 parts of folium artemisiae argyi extract, 15 parts of volatile oil of ligusticum wallichii, 8 parts of eugenol, 12 parts of angelica dahurica powder, 6 parts of menthol, and 10 parts of glycyrrhiza glabra extract by weight in absolute ethanol and stir evenly.

[0045] Step 2: Add 30 parts of nano-emulsifying matrix sodium polyoxyethylene ether sulfosuccinate and sonicate for 30 min. Prepare sodium polyoxyethylene ether sulfosuccinate in the same way as in Example 1.

[0046] Step 3: Add 3 parts of penetration enhancer azone and 10 parts of natural moisturizing factors urea and sodium hyaluronate (2:1), and continue stirring for 1 hour to obtain a uniform ointment.

[0047] Step 4: Uniformly apply the prepared ointment on the medical non-woven fabric, with the thickness controlled between 0.5 - 1 mm. Then place it in a dry environment. After drying is completed, cover it with release paper and cut it into circular patches with a diameter of 5 cm.

[0048] Comparative Example 1

[0049] The difference between this comparative example and Example 1 is that in Step 2, the nano-emulsion matrix is not added, and the remaining steps are the same as those in Example 1.

[0050] Comparative Example 2

[0051] The difference between this comparative example and Example 1 is that in Step 3, the penetration enhancer is not added, and the remaining steps are the same as those in Example 1.

[0052] Comparative Example 3

[0053] The difference between this comparative example and Example 1 is that in Step 2, the nano-emulsion matrix is not added, and in Step 3, the penetration enhancer is not added, and the remaining steps are the same as those in Example 1.

[0054] Comparative Example 4

[0055] Dingguier Umbilical Patch (Yabao Pharmaceutical Group Co., Ltd.)

[0056] Test Example 1

[0057] Clinical data research

[0058] Select 200 child patients with abdominal pain caused by various etiologies such as cold-damp blockage and qi stagnation and blood stasis. Randomly divide them into 4 groups, with 50 people in each group. Use the traditional Chinese medicine patches provided in Example 1, Example 2, Comparative Example 1, Comparative Example 2, Comparative Example 3, and Comparative Example 4 (using Dingguier Umbilical Patch (Yabao Pharmaceutical Group Co., Ltd.)), and apply them to the umbilicus in the same method. Each application lasts for 4 - 6 hours, once a day, and continuously use for 3 days. Record the physiotherapy effect, as shown in Table 1.

[0059] Table 1 Effective rate of clinical data research

[0060] Experimental group Cured / case Effective / case Ineffective / case Total effective rate / % Example 1 43 3 4 92 Example 2 41 5 4 92 Comparative example 1 35 7 8 84 Comparative example 2 34 8 8 82 Comparative example 3 30 5 15 70 Comparative example 4 27 8 15 70

[0061] As can be seen from the data in Table 1, the treatment effects of Example 1 and Example 2 are significantly better than those of Comparative Example 1, Comparative Example 2, Comparative Example 3, and Comparative Example 4. In the clinical data study, the total effective rate of Example 1 is 92%, with 43 cases cured, 3 cases showing improvement, and 4 cases ineffective; the total effective rate of Example 2 is 92%, with 41 cases cured, 5 cases showing improvement, and 5 cases ineffective. The total effective rates of Comparative Example 1, Comparative Example 2, Comparative Example 3, and Comparative Example 4 are 84%, 82%, 70%, and 70% respectively, and the ineffective cases are 8 cases, 8 cases, 15 cases, and 15 cases respectively. This indicates that Example 1 and Example 2 are more excellent in terms of cure rate, total effective rate, and reducing ineffective treatment, and the treatment effect is more ideal.

[0062] Test Example 2

[0063] Transdermal Penetration Test:

[0064] In this test, the total flavonoids in the traditional Chinese medicine patch were used as the test index, and the HPLC method was used to detect the total flavonoid quality in the traditional Chinese medicine transdermal patch sample of the present invention. Healthy SD rats were sacrificed by decapitation, the abdominal hair of the rats was removed with an electric razor, the abdominal rat skin was peeled and treated, and the treated abdominal rat skin was fixed between the sample pool and the receiving pool. The traditional Chinese medicine transdermal patch prepared by the present invention was applied to the stratum corneum of the mouse (the contact area of the stratum corneum of the SD rat with the drug-loading layer was 8 cm 2 ); a transdermal test was carried out on a TP-6 transdermal diffusion instrument. The instrument was set with 6 diffusion cells at the same time. The cell structure was a Franz cell, and the volume of each receiving cell was pre-calibrated, and the volume of each cell was 15 mL; 0.9 wt% physiological saline was prepared as the receiving solution, the sample pool was fixed, and the temperature was kept constant at (32 ± 0.5) °C. Samples were taken at 1, 2, 4, 6, and 8 hours respectively, 0.5 mL was taken each time, and an equal volume of the receiving solution was replenished. The concentration of total flavonoids in the receiving solution was detected by the HPLC method, and the cumulative transmittance Q of total flavonoids was calculated by Formula 1. The test results are shown in Table 2.

[0065] Formula 1 is as follows:

[0066]

[0067] Among them: V0 is the total sampling volume, C i and Cn are the drug mass concentrations (mg / mL) measured at the i-th and n-th time points during sampling, V i is the sampling volume (mL), and m represents the total mass of total flavonoids in the sample.

[0068] Test Example 3

[0069] Allergy Test:

[0070] 120 healthy mice from different litters, with an equal number of males and females, were divided into 6 groups, corresponding to the six test groups of Example 1, Example 2, Example 3, Comparative Example 1, Comparative Example 2, and Comparative Example 3 respectively. Using an electric razor, carefully remove the hair on the left and right sides of the mouse abdomen without damaging the skin of the mouse. The area of the hair removal area on each side is 3.5 cm × 3.5 cm; the blank control for the test and the test are carried out by comparing the left and right sides of the same receptor. Apply an equal amount of physiological saline on the left side and cover and fix it with gauze and tape. Apply the traditional Chinese medicine transdermal patch prepared by the present invention on the right side, and conduct the drug administration test 20 times. The initial drug administration time is 1 hour, the subsequent drug administration times are all 8 hours, the interval time between drug administrations is 12 hours, and after the drug administration is completed, clean the surface of the drug administration residue, and observe and record the allergic reaction indicators such as erythema and edema at the drug administration site on the mouse skin. The results are shown in Table 2:

[0071] Table 2 Transdermal filtration and allergic reaction

[0072] Experimental group Cumulative permeation rate Q in 8 hours / % Allergic Example 1 98.5 No erythema, edema Example 2 97.9 No erythema, edema Example 3 98.2 No erythema, edema Comparative example 1 85.7 No erythema, edema Comparative example 2 82.9 No erythema, edema Comparative example 3 69.3 No erythema, edema

[0073] It can be seen from the data in Table 2 the 8-hour cumulative permeation rate and allergic test conditions of Examples 1-3 and Test Examples 1-3. Among them, the 8-hour cumulative permeation rates of Examples 1-3 are 98.5%, 97.9%, and 98.2% respectively, and the 8-hour cumulative permeation rates of Test Examples 1-3 are 85.7%, 82.9%, and 69.3% respectively, and no allergic conditions such as erythema and edema occurred in both the examples and the test examples. This indicates that the 8-hour cumulative permeation rate of Examples 1-3 is better than that of Test Examples 1-3, and adding a nanoemulsion matrix in Comparative Example 1 and adding a penetration enhancer in Comparative Example 2 are better than not adding a nanoemulsion matrix and a penetration enhancer in Comparative Example 3.

[0074] Result analysis

[0075] Optimized drug compatibility: For different causes of children's abdominal pain, the drug combination was adjusted, enhancing the pertinence and improving the curative effect.

[0076] High-efficiency transdermal absorption technology: Introducing advanced transdermal absorption technology, improving the penetration efficiency of the drug, enabling the drug to reach the lesion faster and shortening the onset time.

[0077] Adding natural moisturizing factors and anti-irritant ingredients: By adding natural moisturizing factors, reducing skin irritation, and enhancing the comfort and safety of the patch, especially suitable for children.

[0078] Wide applicability: The patch is applicable to children of different ages, can deal with abdominal pain caused by various causes, and has wide clinical application value.

[0079] Social benefits: By improving the curative effect and safety, reducing the treatment cycle and side effects of children's abdominal pain, it has significant social benefits.

[0080] In summary, in embodiments 1-3 of the present invention, comprehensive optimizations have been carried out in aspects such as drug compatibility, transdermal absorption, safety, and applicability, significantly improving the clinical effect and social value of traditional Chinese medicine patches.

[0081] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

[0082] The above description of the present invention and its embodiments is not restrictive. What is shown in the drawings is only one of the embodiments of the present invention, and the actual application is not limited thereto. Generally speaking, if those of ordinary skill in the art are inspired by it and, without departing from the purpose of the present invention, design similar methods and embodiments to this technical solution without creative efforts, they should all fall within the protection scope of the present invention.

Claims

1. An external traditional Chinese medicine patch for relieving children's abdominal pain, characterized in that: It is composed of the following components in parts by weight: 5-25 parts of Artemisia argyi extract, 2-20 parts of volatile oil of Ligusticum chuanxiong, 2-10 parts of eugenol, 3-15 parts of Angelica dahurica powder, 1-8 parts of menthol, 2-12 parts of licorice extract, 10-30 parts of nano-emulsifying matrix, 1-3 parts of penetration enhancer, and 2-12 parts of natural moisturizing factor.

2. The external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 1, characterized in that: It is composed of the following components in parts by weight: 10-20 parts of Artemisia argyi extract, 5-15 parts of volatile oil of Ligusticum chuanxiong, 3-8 parts of eugenol, 6-12 parts of Angelica dahurica powder, 2-6 parts of menthol, 4-10 parts of licorice extract, 20-30 parts of nano-emulsifying matrix, 1-3 parts of penetration enhancer, and 6-10 parts of natural moisturizing factor.

3. The external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 2, wherein: The natural moisturizing factor is composed of urea and sodium hyaluronate mixed in a mass ratio of 2:

1.

4. The external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 3, characterized in that: The penetration enhancer is laurocapram.

5. The external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 4, characterized in that: The nano-emulsifying matrix is sodium polyoxyethylene ether sulfosuccinate.

6. The external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 5, wherein: The preparation method of sodium polyoxyethylene ether sulfosuccinate includes the following steps: Cetyl polyoxyethylene ether, succinic anhydride, triethylamine, and 4-dimethylaminopyridine react in dichloromethane at 30 °C for 8 hours to obtain Compound 2. Compound 2 reacts with chlorosulfonic acid in dichloromethane at room temperature for 8 hours, and sodium hydroxide with a molar ratio of 1 is added to form a salt to generate sodium sulfonate salt. Then, it is recrystallized with ethanol at 80 °C to obtain sodium polyoxyethylene ether sulfosuccinate.

7. The external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 6, characterized in that: The molar ratio of cetyl polyoxyethylene ether, succinic anhydride, triethylamine, and 4-dimethylaminopyridine is 1:(1.1-1.3):(0.04-0.06), and the molar ratio of Compound 2 to chlorosulfonic acid is 1:1.

2.

8. A preparation method of an external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 1, characterized in that: The said preparation method includes the following steps: Step 1: Dissolve Artemisia argyi extract, volatile oil of Ligusticum chuanxiong, eugenol, Angelica dahurica powder, menthol, and licorice extract in absolute ethanol. Step 2: After stirring evenly, add the nano-emulsifying matrix. Step 3: Add the penetration enhancer and natural moisturizing factor, and continue stirring for 1 hour to obtain a uniform ointment. Step 4: Coat the ointment on a medical non-woven fabric, dry it, cover it with a release paper, and cut it into the specifications of a patch.

9. The preparation method of an external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 8, characterized in that: Ultrasonic for 30 min after adding the nano-emulsifying matrix.

10. The preparation method of an external traditional Chinese medicine patch for relieving children's abdominal pain according to claim 9, characterized in that: The thickness on the said medical non-woven fabric in Step 3 is 0.5-1 mm.

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