Traditional Chinese medicine ointment for preventing relapse of infantile asthma and preparation method of traditional Chinese medicine ointment

Abstract

The invention relates to the technical field of traditional Chinese medicine plasters, in particular to a traditional Chinese medicine ointment for preventing relapse of infantile asthma and a preparation method thereof.The traditional Chinese medicine ointment is characterized by sequentially comprising a protective backing layer, a medicine storage layer, a controlled release film layer and an application bonding layer from top to bottom; the traditional Chinese medicine plaster provided by the invention overcomes the defect that the traditional oral traditional Chinese medicine is easily influenced by a first-pass effect and individual differences through an external transdermal administration mode, can continuously maintain efficient medicine concentration at an application part and realize long-acting slow release, and the synergistic effect of the nano micro-emulsion medicine carrying system and the controlled release film layer can realize the sustained release effect of the traditional Chinese medicine. According to the traditional Chinese medicine plaster disclosed by the invention, the stable release of effective components of the medicine is ensured, the penetration rate of the medicine on a skin barrier is also remarkably improved, so that the treatment depth and the action durability of the plaster are enhanced, and meanwhile, the traditional Chinese medicine plaster aims at the pathological mechanism of infantile asthma, relieves airway inflammation, reduces airway hyperresponsiveness and mucus secretion, and has a remarkable curative effect on infantile asthma. The acute attack frequency of asthma can be obviously reduced, and the remission period is prolonged.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine plasters, and particularly relates to a traditional Chinese medicine plaster for preventing recurrence of childhood asthma and a preparation method thereof. Background Art

[0002] Bronchial asthma is a respiratory disease characterized by chronic airway inflammation, airway hyperresponsiveness, and reversible airflow limitation. Clinically, it is mainly manifested as repeated coughing, wheezing, and chest tightness, which seriously affect the physical and mental development and quality of life of children. Asthma is characterized by protracted recurrence, susceptibility to multiple attacks, a long treatment cycle, and great management difficulty, especially in the pediatric population. In terms of the pathological mechanism, the nuclear factor-kB (NF-kB) and NLRP3 inflammasome signaling pathways play a key role in airway inflammation: over-activated NF-kB upregulates inflammatory factors such as IL-1β and TNF-α, and the NLRP3 inflammasome promotes the maturation of cytokines such as IL-18, synergistically aggravating airway injury and mucus secretion, forming a persistent inflammatory basis target. In recent years, a number of studies have regarded the NF-kB / NLRP3 inflammatory axis as the key regulatory pathway for the continuous progression and repeated attacks of bronchial asthma.

[0003] Western medicine commonly uses inhaled corticosteroids (ICS), long-acting β2-receptor agonists, and leukotriene receptor antagonists for maintenance treatment, which can improve symptoms in the short term. However, long-term use of ICS can cause the annual growth rate of children to slow down by about 0.48 cm and the cumulative adult height to decrease by about 0.6 cm on average. Moreover, the compliance is poor, and the acute exacerbation and recurrence are high after drug withdrawal, making it difficult to balance the efficacy and safety; the operation of the inhalation device is complex, which further reduces the compliance of children. Traditional Chinese medicine shows unique advantages in the prevention and treatment of pediatric respiratory diseases. The hospital preparation "Xiao'er Xiaokechuan Capsule" (derived from the experience formula of Professor Wang Lie, mainly containing Fritillaria cirrhosa, Scutellaria baicalensis, Lonicera japonica, etc.) can reduce airway inflammation by inhibiting the NF-kB / NLRP3 pathway and significantly reduce airway hyperresponsiveness and mucus secretion in asthmatic model mice; "Xiao'er Kangyan Capsule" has good efficacy and safety in improving throat swelling, pain, and fever, providing an important basis for acute respiratory infections in traditional Chinese medicine pediatrics.

[0004] However, most existing traditional Chinese medicine interventions are mainly oral. After being absorbed by the gastrointestinal tract, they are distributed throughout the body, and the drug concentration targeting the airway is insufficient. Moreover, they are greatly affected by the first-pass effect and individual differences, and the continuous prevention effect is not good. The external plaster dosage form is characterized by transdermal drug delivery, with advantages such as a small first-pass effect, continuous release, and high compliance, especially suitable for long-term use in children. Currently, there is an obvious gap in traditional Chinese medicine plaster products specifically for preventing recurrence of childhood asthma, which has extremely high clinical application value and industrialization prospects. Based on the above deficiencies of the existing technology, the present invention provides a traditional Chinese medicine plaster for preventing recurrence of childhood asthma and a preparation method thereof, which can maintain a high drug concentration locally, continuously release, and improve treatment compliance. Summary of the Invention

[0005] In view of the deficiencies of the prior art, the present invention provides a traditional Chinese medicine paste for preventing recurrence of pediatric asthma and its preparation method, solving the problems put forward in the background art.

[0006] The above technical object of the present invention is achieved through the following technical solutions:

[0007] A traditional Chinese medicine paste for preventing recurrence of pediatric asthma, which sequentially includes from top to bottom:

[0008] A protective backing layer, composed of polyester non-woven fabric, with a grammage of 25 g / m 2 ;

[0009] A drug reservoir layer, formed by mixing medical acrylic pressure-sensitive adhesive and nano-microemulsion drug-loaded particles in a mass ratio of 1:1. The mass composition of the nano-microemulsion drug-loaded particles is: fritillaria cirrhosa extract powder 10 wt%, scutellaria baicalensis extract powder 8 wt%, honeysuckle flower extract powder 7 wt%, artificial bezoar 1 wt%, pearl powder 2 wt%, propylene glycol 10 wt%, an oil phase composed of isopropyl palmitate and ethanol in a volume ratio of 3:1 30 vol%, an emulsifier composed of Tween-80 and Span-80 in a volume ratio of 3:1 5 vol%, and the rest is deionized water; the average particle size of the microemulsion is 100 nm ± 10 nm;

[0010] A controlled-release membrane layer, prepared by dissolving polyvinyl alcohol and sodium carboxymethyl cellulose in a mass ratio of 7:3 in 70 vol% ethanol, coating and drying to form a composite film with a porosity of 20% to 30% and a film thickness of 30 μm ± 5 μm after drying;

[0011] An application adhesive layer for fixing the plaster on the skin.

[0012] Furthermore, the nano-microemulsion drug-loaded particles are prepared through the following steps:

[0013] Mix isopropyl palmitate and ethanol in a volume ratio of 3:1 as the oil phase;

[0014] Mix propylene glycol and deionized water in a volume ratio of 1:5 as the water phase;

[0015] Add the oil phase to the water phase at a rate of 1 mL / s under the condition of 6000 rpm and shear emulsify at 15000 rpm for 15 min, and the average particle size of the microemulsion is 100 nm ± 10 nm.

[0016] Furthermore, the mass ratio of the medical acrylic pressure-sensitive adhesive to the nano-microemulsion drug-loaded particles is 1:1.

[0017] Furthermore, the controlled-release membrane layer is prepared through the following steps:

[0018] Dissolve polyvinyl alcohol and sodium carboxymethyl cellulose in 70 vol% ethanol according to a mass ratio of 7:3 and stir evenly;

[0019] Coat the solution on the surface of the plaster with a 30 μm doctor blade and place it at 25 °C to dry naturally for 30 min to obtain a composite film.

[0020] This application also provides a preparation method of a traditional Chinese medicine plaster for preventing recurrence of pediatric asthma, including the following steps:

[0021] S1. Mix the crude powder of Fritillaria cirrhosa, Scutellaria baicalensis, and Lonicera japonica in a mass ratio of 10:8:7, pulverize it, and pass it through a 75 μm sieve;

[0022] S2. Prepare a nanoemulsion. Specifically, mix isopropyl palmitate and ethanol in a volume ratio of 3:1 as the oil phase, and mix propylene glycol and deionized water in a volume ratio of 1:5 as the water phase. Slowly add the oil phase to the water phase at a rate of 1 mL / s under the condition of 6000 rpm, and shear emulsify at 15000 rpm for 15 min to obtain a microemulsion with an average particle size of 100 nm ± 10 nm;

[0023] S3. Mix the traditional Chinese medicine powder obtained in step S1 and the nanoemulsion obtained in step S2 in a mass ratio of 1:3, and stir at 50 °C and 500 rpm for 40 min to form a drug reservoir paste;

[0024] S4. Mix the paste obtained in step S3 and a medical acrylic pressure-sensitive adhesive in a mass ratio of 1:1, and homogenize and stir at 50 °C and 300 rpm for 30 min to obtain a uniform mixture;

[0025] S5. Use a doctor blade to evenly coat the mixture obtained in step S4 on a polyester non-woven fabric backing, and dry it at a temperature of 60 °C and a relative humidity not exceeding 30% for 20 min;

[0026] S6. Prepare a controlled-release membrane layer. Specifically, dissolve polyvinyl alcohol and sodium carboxymethyl cellulose in 70% by volume of ethanol according to a mass ratio of 7:3, stir evenly, coat it on the surface of the plaster with a 30 μm doctor blade, and dry it at 25 °C for 30 min to form a controlled-release composite membrane with a porosity of 20 - 30% and a thickness of 30 μm ± 5 μm;

[0027] S7. Cut the dried plaster into pieces with an area of 10 cm per piece 2 , sterilize it with γ-rays at a dose of 25 kGy, and then carry out packaging.

[0028] Further, in step S5, the doctor blade thickness is 200 μm - 300 μm.

[0029] The present application also provides a method for administering a traditional Chinese medicine paste for preventing recurrence of pediatric asthma, comprising the following steps:

[0030] a), successively clean the skin of the Tanzhong acupoint, Feishu acupoint, and Dingchuan acupoint on the chest and back of the child with 75% medical alcohol cotton balls for 1 minute each, and then place them in an environment at 25°C with a relative humidity not exceeding 60% to air dry naturally for 2 minutes;

[0031] b), remove the protective backing layer, accurately apply the paste on the above-mentioned acupoints, and gently press with fingers for 5 seconds;

[0032] c), fix it once along the edge of the paste with a breathable medical tape;

[0033] d), remove it after continuous application for 8 hours, and repeat the application at least 4 hours later;

[0034] e), repeat steps b) to d), and continuous application for 4 weeks is regarded as one course of treatment.

[0035] Further, after step d), clean the application site with normal saline and apply a moisturizing lotion without irritating ingredients for 1 minute to reduce skin irritation.

[0036] In summary, the present invention mainly has the following beneficial effects:

[0037] 1. The traditional Chinese medicine paste provided by the present invention overcomes the deficiencies of traditional oral Chinese medicine being easily affected by the first-pass effect and individual differences through the external transdermal drug delivery method. It can continuously maintain a high drug concentration at the application site to achieve long-acting sustained release. The synergistic effect of the used nanoemulsion drug delivery system and the controlled release membrane layer not only ensures the stable release of active ingredients such as Fritillaria cirrhosa, Scutellaria baicalensis, and Lonicera japonica, but also significantly improves the penetration rate of the drug through the skin barrier, thereby enhancing the treatment depth and action persistence of the paste. At the same time, the reasonable ratio of the polyester non-woven protective backing layer and the medical acrylic pressure-sensitive adhesive not only ensures stable adhesion and comfort during the application process, but also facilitates good compliance of children during daily activities.

[0038] 2. The traditional Chinese medicine paste of the present invention targets the pathological mechanism of pediatric asthma and relies on the precise inhibitory effect of nanoemulsion on the NF-kB / NLRP3 pathway in vitro and in vivo. It can effectively down-regulate the expression of key inflammatory factors such as IL-1β, TNF-α, and IL-18, thereby alleviating airway inflammation, reducing airway hyperresponsiveness and mucus secretion. Clinical or animal model studies show that this paste can significantly reduce the frequency of acute asthma attacks, prolong the remission period, and has no obvious systemic adverse reactions, with good safety. The drug delivery method with convenient application and simple operation greatly improves the medication compliance of children, providing a safe, efficient, and easy-to-promote new traditional Chinese medicine external treatment solution for preventing and controlling the recurrence of childhood bronchial asthma. Description of the Drawings

[0039] Figure 1 It is the flow chart of the preparation method of the traditional Chinese medicine paste for preventing the recurrence of pediatric asthma in Embodiment 1 of the present invention. Detailed implementation manners

[0040] In order to make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Apparently, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the described embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0041] The following embodiments are used to illustrate the present invention, but cannot be used to limit the protection scope of the present invention. The conditions in the embodiments can be further adjusted according to specific conditions, and simple improvements to the method of the present invention under the premise of the concept of the present invention all fall within the protection scope required by the present invention.

[0042] Embodiment 1: A traditional Chinese medicine paste for preventing the recurrence of pediatric asthma

[0043] I. Reagents and materials: Fritillaria cirrhosa D. Don extraction powder (batch number: CBM202402), Scutellaria baicalensis Georgi extraction powder (batch number: HQ202401), Lonicera japonica Thunb. extraction powder (batch number: JYH202403), artificial bezoar (batch number: RNH202403), pearl powder (batch number: ZHP202402), propylene glycol (AR), isopropyl palmitate (IPLP), ethanol (70 vol%), Tween 80, Span 80, medical acrylic pressure-sensitive adhesive (PSA), polyester non-woven fabric (25 g / m 2 ), polyvinyl alcohol (PVA, Mw≈89000–98000) and sodium carboxymethyl cellulose (CMC-Na). The above materials are all of analytical purity or industrial grade and are filtered through a 0.22 μm filter membrane before use.

[0044] II. Component ratio (calculated based on a total amount of 100 g) is shown in Table 1

[0045] Component wt% Mass / g Fritillaria cirrhosa D. Don extract powder 10.0 10.0 Scutellaria baicalensis Georgi extract powder 8.0 8.0 Lonicera japonica Thunb. extract powder 7.0 7.0 Artificial bezoar 1.0 1.0 Pearl powder 2.0 2.0 Propylene glycol 10.0 10.0 Oil phase (IPLP∶ethanol = 3∶1, 30 vol%) ≈20.0 20.0 Emulsifier (Tween80∶Span80 = 3∶1, 5 vol%) ≈3.3 3.3 Deionized water —— 38.7 Total 100 100

[0046] Table 1 (Note: The volume fractions of the oil phase and the emulsifier are converted to approximate wt%, and the actual weighing can be slightly adjusted according to the density)

[0047] III. Preparation of nanoemulsion

[0048] 1. Premix IPLP (30 mL, ≈15.6 g) and ethanol (10 mL, ≈7.9 g) at a volume ratio of 3:1, and dissolve them in a water bath at 40 °C to form an oil phase;

[0049] 2. Propylene glycol (10 g) and deionized water (50 g) are premixed at a volume ratio of 1:5 and placed in a constant-temperature water bath to form an aqueous phase;

[0050] 3. Start the homogenizer and stir the aqueous phase at 6000 rpm for 2 min to ensure uniformity;

[0051] 4. Slowly add the oil phase from the dropper to the aqueous phase at a rate of 1 mL / s, and simultaneously increase the speed of the homogenizer to 15000 rpm for shear emulsification for 15 min;

[0052] 5. Let it stand at room temperature for 10 min to defoam; take 1 mL of the sample, and use a laser particle size analyzer to measure the average particle size of 100 nm ± 10 nm and PDI < 0.2.

[0053] IV. Preparation of the drug reservoir paste

[0054] 1. Accurately weigh the powder of Fritillaria cirrhosa, Scutellaria baicalensis, and Lonicera japonica (10 g, 8 g, and 7 g respectively), and pass through a 75-μm sieve;

[0055] 2. After mixing the traditional Chinese medicine powders evenly, remove the surface air by means of a vacuum defoaming device;

[0056] 3. Under the conditions of 50 °C and 500 rpm (IKA RCT Basic rotary mixer), slowly add the above nanoemulsion (75 mL, ≈30 g), and continuously stir for 40 min until a smooth and particle-free paste is formed; defoam and take samples for retention.

[0057] V. Preparation of the patch substrate

[0058] 1. Accurately weigh PSA (≈45 g) and add it to the homogenizer bottle at a mass ratio of 1:1 with the paste in step 4 (≈55 g);

[0059] 2. Homogenize and stir at 50 °C and 300 rpm for 30 min to ensure that PSA and the microemulsion paste are fully dispersed; take a small amount and place it on a glass slide to observe the viscosity and fluidity;

[0060] 3. Lay the polyester non-woven fabric flat on the scraping platform and uniformly coat it with a coater (knife gap 250 μm, line speed 0.5 m / min); wait until there is no running on the surface and immediately transfer it to the oven;

[0061] 4. Dry it at 60 °C and a relative humidity of ≤30% for 20 min, and turn it over every 5 min during this period to ensure uniform thickness.

[0062] VI. Preparation of the controlled-release membrane layer

[0063] 1. Prepare the PVA / CMC-Na solution: Weigh 7 g of PVA and 3 g of CMC-Na, and gradually add them to 100 mL of 70 vol% ethanol, and stir until it is clear and transparent;

[0064] 2. Use a doctor blade coater (blade edge 30 μm, line speed 0.3 m / min) to evenly coat the solution on the medicated surface of the plaster. The ambient temperature is 25 °C and the RH is 50%. Allow it to dry naturally for 30 min;

[0065] 3. After drying, observe the cross-section with an electron microscope (SEM, ZEISS EVO18): the film thickness is 30 μm ± 5 μm, the pore size distribution is uniform, and the porosity is 20% - 30%.

[0066] VII. Slitting and Sterilization

[0067] On a clean workbench, cut the dried patch into 2 cm × 5 cm (10 cm 2 ) units, representing 10 patches per box. Put them into a gamma-ray sterilizer, set the dose to 25 kGy, and irradiate for 6 h; after taking them out, seal them into an aluminum-plastic composite bag and package them with nitrogen filling.

[0068] VIII. Process Monitoring and Quality Inspection

[0069] Particle size and distribution: Take samples 3 times for each batch, with an average of 100 nm ± 10 nm and PDI < 0.2;

[0070] Thickness and porosity: Randomly select 10 places to measure the thickness, 30 μm ± 5 μm; the porosity is 20% - 30%;

[0071] Adhesion: The peel strength measured by a PEKOE tester is 0.15 N / cm ± 0.02 N / cm, meeting the comfort requirements for children's application;

[0072] Appearance and stability: At 25 °C / 60% RH for 3 months, there are no changes in color, odor, and structure.

[0073] Reference Figure 1 As shown, the specific preparation method of the traditional Chinese medicine plaster for preventing the recurrence of childhood asthma includes the following steps:

[0074] S1. Mix the crude powder of Fritillaria cirrhosa, Scutellaria baicalensis, and Lonicera japonica in a mass ratio of 10:8:7, pulverize them, and pass through a 75 μm sieve;

[0075] S2. Prepare a nanoemulsion. Specifically, mix isopropyl palmitate and ethanol in a volume ratio of 3:1 as the oil phase, and mix propylene glycol and deionized water in a volume ratio of 1:5 as the water phase. Slowly drop the oil phase into the water phase at a rate of 1 mL / s under the condition of 6000 rpm, and at the same time shear and emulsify at 15000 rpm for 15 min to obtain a microemulsion with an average particle size of 100 nm ± 10 nm;

[0076] S3. Mix the traditional Chinese medicine powder obtained in step S1 and the nano microemulsion obtained in step S2 at a mass ratio of 1:3, and stir for 40 min at 50 °C and 500 rpm to form a drug reservoir paste;

[0077] S4. Mix the paste obtained in step S3 and the medical acrylic pressure-sensitive adhesive at a mass ratio of 1:1, and homogenize and stir for 30 min at 50 °C and 300 rpm to obtain a uniform mixture;

[0078] S5. Use a spatula to evenly coat the mixture obtained in step S4 on a polyester non-woven fabric backing, and dry for 20 min at a temperature of 60 °C and a relative humidity not exceeding 30%;

[0079] S6. Prepare a controlled-release membrane layer. Specifically, dissolve polyvinyl alcohol and sodium carboxymethyl cellulose in ethanol with a volume fraction of 70% at a mass ratio of 7:3, stir evenly, then coat it on the surface of the plaster with a 30-μm spatula, and dry at 25 °C for 30 min to form a controlled-release composite membrane with a porosity of 20-30% and a thickness of 30 μm ± 5 μm;

[0080] S7. Cut the dried plaster into pieces with an area of 10 cm 2 , sterilize it with γ-rays at a dose of 25 kGy, and then carry out packaging.

[0081] Example 2: Clinical control study (ICS maintenance therapy vs traditional Chinese medicine plaster)

[0082] To evaluate the differences between the plaster of the present invention and the maintenance therapy with commonly used inhaled corticosteroids (ICS) in Western medicine for the prevention of recurrence in children with asthma, a prospective, randomized, open-label controlled clinical study was conducted.

[0083] I. Research subjects

[0084] Inclusion criteria: Children with mild to moderate persistent bronchial asthma aged 6-12 years, with ≥2 acute attacks in the past six months;

[0085] Exclusion criteria: Severe systemic diseases, skin lesions or contraindications to application;

[0086] A total of 120 cases were included and randomly divided into two groups, with 60 cases in each group.

[0087] II. Research design, as shown in Table 2

[0088]

[0089] Table 2

[0090] III. Index evaluation

[0091] Annual growth rate: Calculated as height increment / follow-up time;

[0092] Lung function: The FEV1 / FVC and FEV1% predicted value were measured using a portable lung function instrument;

[0093] Compliance: Parents filled out the application or inhalation diary, and compliance = actual number of completions ÷ planned number of times × 100%;

[0094] Acute recurrence rate: The number of emergency department visits or hospitalizations due to asthma exacerbation per case.

[0095] IV. Results, as shown in Table 3

[0096] Index ICS group (n = 60) Patch group (n = 60) Difference between groups Annual growth rate (cm / year) 5.2±0.6 6.1±0.5 ↑0.9 cm / year (p < 0.01) <![CDATA[FEV1% predicted value (%)]]> 82.3±5.4 84.7±4.8 ↑2.4％(p<0.05) Compliance (%) 68±12 91±6 ↑23％(p<0.01) Annual recurrence rate (times / person·year) 2.3±0.8 1.1±0.5 ↓ 1.2 times (p < 0.01)

[0097] Table 3

[0098] As shown in Table 3, compared with long-term ICS inhalation, the annual growth rate of children in the plaster group was significantly faster, reducing growth inhibition by approximately 0.48 cm / year;

[0099] The improvement in lung function was comparable, the compliance was significantly higher, and the acute recurrence rate decreased by nearly 52%;

[0100] It was proved that the external plaster was superior to traditional ICS maintenance therapy in terms of safety, compliance, and prevention of recurrence.

[0101] Example 3: Comparative experiment of traditional Chinese medicine oral preparations (mouse model)

[0102] To compare with the efficacy of the traditional Chinese medicine plaster of the present invention, two representative traditional Chinese medicine pediatric oral preparations in the background technology were selected, namely "Xiao'er Xiao Ke Chuan Capsule" (hereinafter referred to as Group A, the formula includes Fritillaria cirrhosa, Scutellaria baicalensis, honeysuckle, etc.) and "Xiao'er Kang Yan Capsule" (hereinafter referred to as Group B). In the ovalbumin (OVA)-induced mouse model of bronchial asthma, the regulatory effects on the NF-kB / NLRP3 inflammatory signaling pathway and airway hyperresponsiveness were investigated.

[0103] I. Materials and methods

[0104] Animal model:

[0105] BALB / c mice aged 6 - 8 weeks were selected and randomly divided into 5 groups, with 8 mice in each group, specifically as follows:

[0106] Normal control group (without modeling);

[0107] Model control group (established asthma model, without treatment);

[0108] Group A (Xiao'er Xiao Ke Chuan Capsule);

[0109] Group B (Xiao'er Kang Yan Capsule);

[0110] Plaster group (Example 1);

[0111] Modeling method: An ovalbumin-induced mouse model of bronchial asthma was established.

[0112] Drug administration method and dosage:

[0113] Groups A and B: Oral administration at 200 mg per kilogram of body weight once a day;

[0114] Patch group: The traditional Chinese medicine patch obtained in Example 1 was applied to the back every day, with an area of 2×2 cm, for 8 hours continuously;

[0115] Continuous treatment for 14 days

[0116] Detection indicators:

[0117] Airway hyperresponsiveness (AHR): Induced by methacholine, and the Penh value was recorded;

[0118] Inflammatory factors in bronchoalveolar lavage fluid (BALF): IL-1β, TNF-α, IL-18;

[0119] Protein expression levels of NF-kB p65 and NLRP3 in lung tissue (detected by Western blotting, relative gray value).

[0120] II. Experimental results, as shown in Table 4

[0121]

[0122] Table 4

[0123] It can be seen from Table 4 that:

[0124] 1. Both Xiao'er Xiaokechuan Capsule and Xiao'er Kangyan Capsule can effectively inhibit the abnormal activation of the NF-κB / NLRP3 pathway in the OVA-induced asthma model, reduce the levels of inflammatory factors and airway hyperresponsiveness, demonstrating good traditional Chinese medicine intervention effects;

[0125] 2. In comparison, the traditional Chinese medicine patch of the present invention shows a stronger inhibitory effect under the same experimental conditions. Its airway reactivity and inflammatory factor levels are significantly lower than those of the oral group, indicating that the transdermal drug delivery route can achieve better local drug effect maintenance and inflammation control;

[0126] 3. This result further verifies the application advantages of the patch dosage form in preventing recurrence of pediatric asthma, especially in terms of improving compliance and reducing systemic side effects, with significant characteristics and application potential.

[0127] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A traditional Chinese medicine paste for preventing recurrence of pediatric asthma, characterized in that, The traditional Chinese medicine paste sequentially includes the following from top to bottom: Protective backing layer, composed of polyester non-woven fabric, with a grammage of 25 g / m 2 ; A drug reservoir layer, which is formed by mixing a medical acrylic pressure-sensitive adhesive and nano-microemulsion drug-loaded particles in a mass ratio of 1:

1. The mass composition of the nano-microemulsion drug-loaded particles is as follows: 10 wt% of fritillaria cirrhosa extraction powder, 8 wt% of scutellaria baicalensis extraction powder, 7 wt% of honeysuckle flower extraction powder, 1 wt% of artificial bezoar, 2 wt% of pearl powder, 10 wt% of propylene glycol, 30 vol% of an oil phase composed of isopropyl palmitate and ethanol in a volume ratio of 3:1, 5 vol% of an emulsifier composed of Tween-80 and Span-80 in a volume ratio of 3:1, and the balance being deionized water; the average particle size of the microemulsion is 100 nm ± 10 nm; A controlled-release membrane layer, which is prepared by dissolving polyvinyl alcohol and sodium carboxymethylcellulose in a mass ratio of 7:3 in 70 vol% ethanol, coating and then drying to form a composite film with a porosity of 20% to 30% and a dried film thickness of 30 μm ± 5 μm; An application adhesive layer for fixing the plaster on the skin.

2. The traditional Chinese medicine plaster according to claim 1, characterized in that, The nano-microemulsion drug-loaded particles are prepared through the following steps: Mix isopropyl palmitate and ethanol in a volume ratio of 3:1 as an oil phase; Mix propylene glycol and deionized water in a volume ratio of 1:5 as a water phase; Add the oil phase to the water phase at a rate of 1 mL / s under the condition of 6000 rpm and shear emulsify at 15000 rpm for 15 min, and the average particle size of the microemulsion is 100 nm ± 10 nm.

3. The traditional Chinese medicine plaster according to claim 1, characterized in that, The mass ratio of the medical acrylic pressure-sensitive adhesive to the nano-microemulsion drug-loaded particles is 1:

1.

4. The traditional Chinese medicine plaster according to claim 1, wherein The controlled-release membrane layer is prepared through the following steps: Dissolve polyvinyl alcohol and sodium carboxymethylcellulose in a mass ratio of 7:3 in 70 vol% ethanol and stir evenly; Coat the solution on the surface of the plaster with a 30-μm doctor blade and place it at 25°C for natural drying for 30 min to obtain a composite film.

5. A method for preparing the traditional Chinese medicine plaster described in claim 1, characterized in that, Including the following steps: S1. Mix the crude powders of fritillaria cirrhosa, scutellaria baicalensis, and honeysuckle flower in a mass ratio of 10:8:7, pulverize them, and pass through a 75-μm sieve; S2. Prepare a nano-microemulsion. Specifically, mix isopropyl palmitate and ethanol in a volume ratio of 3:1 as an oil phase, mix propylene glycol and deionized water in a volume ratio of 1:5 as a water phase, slowly drop the oil phase into the water phase at a rate of 1 mL / s under the condition of 6000 rpm, and at the same time shear emulsify at 15000 rpm for 15 min to obtain a microemulsion with an average particle size of 100 nm ± 10 nm; S3. Mix the traditional Chinese medicine powder obtained in step S1 and the nano-microemulsion obtained in step S2 in a mass ratio of 1:3, and stir at 50°C and 500 rpm for 40 min to form a drug reservoir paste; S4. Mix the paste obtained in step S3 and the medical acrylic pressure-sensitive adhesive in a mass ratio of 1:1, and homogenize and stir at 50°C and 300 rpm for 30 min to obtain a uniform mixture; S5. Uniformly coat the mixture obtained in step S4 on a polyester non-woven fabric backing with a doctor blade, and dry it at a temperature of 60°C and a relative humidity of not more than 30% for 20 min; S6. Prepare the controlled-release membrane layer. Specifically, dissolve polyvinyl alcohol and sodium carboxymethyl cellulose in ethanol with a volume fraction of 70% at a mass ratio of 7:3, stir evenly, then coat it on the surface of the plaster with a 30-μm doctor blade, and dry it at 25°C for 30 min to form a controlled-release composite membrane with a porosity of 20-30% and a thickness of 30 μm ± 5 μm. S7. Cut the dried plaster into patches with an area of 10 cm² each 2 , sterilize it with γ-rays at a dose of 25 kGy, and then carry out packaging.

6. The preparation method according to claim 5, characterized in that, In the step S5, the doctor blade thickness is 200 μm - 300 μm.

7. A drug administration method for preventing recurrence of pediatric asthma, characterized in that, It includes the following steps: a). Use 75% medical alcohol cotton balls to clean the skin of the Tanzhong acupoint, Feishu acupoint, and Dingchuan acupoint on the chest and back of children for 1 min each, and then place them in an environment at 25°C with a relative humidity not exceeding 60% to air dry naturally for 2 min. b). Remove the protective backing layer, accurately apply the plaster to the above acupoints, and gently press with fingers for 5 s. c). Fix it once along the edge of the plaster with breathable medical tape. d). Remove it after continuous application for 8 h, and repeat the application at least 4 h later. e). Repeat steps b) - d), and continuous application for 4 weeks is one course of treatment.

8. The administration method according to claim 7, characterized in that, After the step d), wash the application site with normal saline and apply a moisturizing lotion without irritating ingredients for 1 min to reduce skin irritation.

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