High-permeability moxibustion sheet, preparation method and application thereof

Abstract

The application belongs to the technical field of moxibustion pieces, and specifically provides a high-permeability moxibustion piece, a preparation method and application thereof. The preparation method of the high-permeability moxibustion piece comprises the following steps: 1) crushing dry mugwort material, mixing with a solvent to beat pulp, and obtaining a slurry; the solvent is composed of deionized water and dimethyl sulfoxide; 2) dissolving sulfobutyl-beta-cyclodextrin in deionized water, adding an alcohol solution containing beta-caryophyllene, mixing uniformly, then adding potassium hydroxide, and stirring to form an alkaline emulsion; making the alkaline emulsion contact with methanol vapor to perform vapor diffusion crystallization, collecting the crystallization product after the crystallization is completed, washing, drying, and preparing a transdermal enhancer; 3) uniformly mixing the slurry, the transdermal enhancer and pharmaceutically acceptable excipients, low-temperature drying to obtain wet material, and then performing low-temperature nitrogen blowing drying after shaping the wet material, so that the moxibustion piece prepared by the application has the advantage of good transdermal absorption.

Description

Technical Field

[0001] This application belongs to the field of moxibustion tablet technology, and in particular relates to a high-penetration moxibustion tablet, its preparation method, and its application. Background Technology

[0002] Moxibustion is a traditional Chinese medicine external treatment method that uses mugwort leaves as raw material. The heat generated by burning or heating the mugwort leaves, along with the medicinal components, acts on acupoints to achieve effects such as warming the meridians, dispelling cold, and relieving pain. Modern research shows that the therapeutic effect of moxibustion depends on the synergistic effect of the thermal effect, the far-infrared radiation effect, and the transdermal absorption effect of the active ingredients in mugwort leaves. Specifically, the active substances in mugwort leaves must penetrate the skin's stratum corneum barrier to enter the systemic circulation in order to better exert their anti-inflammatory, analgesic, and immunomodulatory pharmacological effects. Therefore, improving the transdermal absorption efficiency of the active ingredients in mugwort leaves is key to enhancing the therapeutic effect of moxibustion.

[0003] The stratum corneum of the skin, composed of highly ordered keratinocytes and an intercellular lipid bilayer, is the primary barrier to transdermal drug absorption. During conventional moxibustion, although the high temperatures generated by combustion can increase the thermal motion of drug molecules and disrupt the lipid arrangement of the stratum corneum to some extent, the thermal effect alone is insufficient to allow highly polar or high molecular weight active ingredients to fully penetrate the skin. Therefore, introducing transdermal penetration enhancers (also known as transdermal absorption enhancers) into moxibustion preparations to reversibly reduce skin barrier resistance and increase transdermal drug penetration has become a commonly used approach in this field.

[0004] An ideal transdermal penetration enhancer should possess characteristics such as strong penetration enhancement, rapid onset of action, low skin irritation, rapid recovery of barrier function after removal, and chemical stability. However, in preparations like moxibustion tablets that require direct application to the skin after combustion or high-temperature heating, transdermal penetration enhancers must also meet stringent requirements for chemical stability and safety under high-temperature conditions. Currently common transdermal penetration enhancers include chemically synthesized transdermal penetration enhancers represented by dimethyl sulfoxide (DMSO) and plant-derived transdermal penetration enhancers represented by natural terpenoids. DMSO has extremely strong penetration enhancement capabilities. Its mechanism involves the formation of hydrogen bonds between the sulfoxide group in the molecule and the polar head groups of stratum corneum lipids, disrupting the tight packing of lipids and increasing the fluidity of the stratum corneum. However, DMSO can be absorbed in large quantities through the skin into the systemic circulation, and the transdermal absorption rate is further accelerated at high temperatures, causing irritation and potential toxicity to the skin and body. Therefore, its application in transdermal drug delivery products is strictly limited. Terpenoids contain heat-sensitive groups such as unsaturated double bonds. In the high-temperature environment generated by the combustion or heating of moxibustion patches, they are highly susceptible to degradation reactions such as free radical chain oxidation, thermal isomerization, and thermal polymerization, leading to loss of penetration-enhancing activity and potentially causing skin sensitization. Furthermore, terpenoids themselves are volatile; if a large amount is lost in the initial stages of use, they cannot provide a synchronous and sustained penetration-enhancing effect throughout the continuous release of the active ingredients in Artemisia argyi. Therefore, natural terpenoid transdermal penetration enhancers suffer from significant drawbacks in terms of chemical stability and functional sustainability under moxibustion conditions.

[0005] To address the aforementioned technical bottlenecks, developing a high-permeability moxibustion patch that can effectively protect transdermal penetration enhancers from thermal degradation under the high-temperature combustion environment of moxibustion, achieve simultaneous controlled release of penetration enhancers and drugs, and possess good skin compatibility and process feasibility is of significant practical importance and industrial value. Summary of the Invention

[0006] To address the above issues, this application provides a high-penetration moxibustion patch, its preparation method, and its application.

[0007] This application first provides a method for preparing a high-penetration moxibustion patch, comprising the following steps: 1) Crush dried Artemisia argyi into powder, mix with solvent and slurry to obtain slurry; the solvent is composed of deionized water and dimethyl sulfoxide; 2) Dissolve sulfobutyl-β-cyclodextrin in deionized water, add an alcohol solution containing β-caryophyllene and mix well, then add potassium hydroxide and stir to form an alkaline emulsion; allow the alkaline emulsion to contact methanol vapor for vapor diffusion crystallization, collect the crystals after crystallization, wash and dry to obtain a transdermal penetration enhancer. 3) Mix the slurry, transdermal penetration enhancer, and pharmaceutically acceptable excipients evenly, dry at low temperature to obtain wet material, and then dry the wet material under low temperature nitrogen blowing after shaping to obtain the final product.

[0008] Furthermore, the mass ratio of deionized water to dimethyl sulfoxide in the solvent is 1:(0.003-0.01).

[0009] As a further preferred embodiment of this application, the mass ratio of deionized water to dimethyl sulfoxide in the solvent can be, for example, 1:0.003, 1:0.004, 1:0.005, 1:0.006, 1:0.007, 1:0.008, 1:0.009, or 1:0.01, more preferably 1:(0.004-0.006). The ratio of deionized water to dimethyl sulfoxide in the solvent determines the polar environment of the slurry and the dissolution efficiency of the endogenous active ingredients of Artemisia argyi.

[0010] Furthermore, the ratio of sulfobutyl-β-cyclodextrin to water is (50-150) g: 1 L.

[0011] As a further preferred embodiment of this application, the ratio of sulfobutyl-β-cyclodextrin to water can be, for example, 50 g:1 L, 60 g:1 L, 70 g:1 L, 80 g:1 L, 90 g:1 L, 100 g:1 L, 110 g:1 L, 120 g:1 L, 130 g:1 L, 140 g:1 L, or 150 g:1 L, more preferably (100-130) g:1 L. The concentration of sulfobutyl-β-cyclodextrin in water directly determines the collision frequency of coordination self-assembly units and the crystal nucleation rate in the alkaline emulsion. Controlling this ratio is key to obtaining a regular porous crystal framework morphology and high encapsulation efficiency.

[0012] Furthermore, the mass ratio of β-caryophyllene to sulfobutyl-β-cyclodextrin is 1:(30-80).

[0013] As a further preferred embodiment of this application, the mass ratio of β-caryophyllene to sulfobutyl-β-cyclodextrin can be, for example, 1:30, 1:35, 1:40, 1:45, 1:50, 1:55, 1:60, 1:65, 1:70, 1:75, or 1:80, more preferably 1:(40-60). The mass ratio of β-caryophyllene to sulfobutyl-β-cyclodextrin directly determines the drug loading and encapsulation efficiency of the final complex. Precisely controlling the amount of guest molecules introduced while ensuring the integrity of the framework structure is crucial to achieving optimal loading saturation of the nanopores and avoiding burst release caused by free drug residues on the surface.

[0014] Furthermore, the mass ratio of potassium hydroxide to sulfobutyl-β-cyclodextrin is 1:(3-8).

[0015] As a further preferred embodiment of this application, the mass ratio of potassium hydroxide to sulfonyl-β-cyclodextrin can be, for example, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, or 1:8, more preferably 1:(4-6). The amount of potassium hydroxide added determines the alkalinity and potassium ion concentration of the reaction system, directly affecting the degree of deprotonation of the hydroxyl groups in the sulfonyl-β-cyclodextrin molecule and the integrity of the K⁺ bridging coordination network.

[0016] Furthermore, the temperature for the vapor diffusion crystallization is 20-30°C, and the time is 48-72 seconds.

[0017] As a further preferred embodiment of this application, specifically, the temperature can be, for example, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃, or 30℃, and the time can be, for example, 48h, 52h, 56h, 60h, 64h, 68h, or 72h. More preferably, the crystallization temperature is 23-27℃, and the crystallization time is 56-68h. The temperature and time of vapor diffusion crystallization together determine the permeation rate of methanol antisolvent into the alkaline emulsion and the crystal growth kinetics. These two parameters are key to obtaining a supported transdermal accelerator with high crystallinity, narrow particle size distribution, and orderly encapsulation of β-caryophyllene molecules in nanopores.

[0018] Furthermore, the pharmaceutically acceptable excipient is selected from at least one of wetting agents, surfactants, and inorganic salts.

[0019] Furthermore, the wetting agent is glycerin, the surfactant is stearate, and the inorganic salt is magnesium sulfate.

[0020] This application provides a highly permeable moxibustion patch, which is prepared using the above-described method.

[0021] This application provides an application of a high-penetration moxibustion patch, wherein the moxibustion patch prepared by the above method is used in traditional Chinese medicine moxibustion products, the traditional Chinese medicine moxibustion products including moxibustion patches or self-heating moxibustion patches.

[0022] Compared with the prior art, this application has the following beneficial effects: This application utilizes a porous crystal framework formed by sulfobutyl-β-cyclodextrin under potassium ion-driven encapsulation of β-caryophyllene, constructing a highly thermally stable loaded transdermal activator. Under high-temperature moxibustion conditions, the confinement effect of the nanopores inhibits the conformational changes required to initiate free radical chain reactions. Simultaneously, the pore walls block mass transfer of ambient oxygen into the pores, thereby inhibiting oxidative degradation pathways and effectively protecting β-caryophyllene. The introduction of sulfobutyl groups endows the framework with suitable hydrophilicity and a negative surface charge, enabling the transdermal activator to be uniformly dispersed in Artemisia argyi slurry. Furthermore, it synergistically maintains tablet moisture with excipients such as glycerin and magnesium sulfate, overcoming the shortcomings of ordinary CD-MOFs in aqueous systems, such as poor stability and poor dispersibility. Meanwhile, on the skin surface, the framework gradually dissociates with hydration, and the encapsulated β-caryophyllene is slowly released at a controlled rate. Its release curve matches the thermal release curve of the endogenous volatile oil of Artemisia argyi, realizing the synchronization of the penetration enhancer and the drug in the time dimension. This allows the transdermal enhancement effect to run through the entire moxibustion process, avoiding the problem of concentrated loss of the penetration enhancer in the early stage of use and insufficient penetration in the middle and late stages of use. Detailed Implementation

[0023] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the embodiments of this application. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0025] When using “including,” “having,” and “contains” as described herein, the intention is to cover non-exclusive inclusion, unless an explicit qualifying term such as “only,” “consisting of,” etc., is used, in which case another component may be added.

[0026] The terms "preferred," "more preferably," "better," and "even better" used in this application refer to embodiments of this application that provide certain beneficial effects under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of this application. That is, in this application, "preferred," "more preferably," "better," and "even better" are merely descriptions of implementations or embodiments with better effects, but do not constitute a limitation on the scope of protection of this application.

[0027] In this application, terms such as "further," "even more," and "particularly" are used for descriptive purposes and indicate differences in content, but should not be construed as limiting the scope of protection of this application.

[0028] In this application, "at least one" means one or more, such as one, two, or more. "Multiple" or "several" means at least two, such as two, three, etc., and "multi-layered" means at least two layers, such as two layers, three layers, etc., unless otherwise explicitly specified. In the description of this application, "several" means at least one, such as one, two, etc., unless otherwise explicitly specified.

[0029] When a numerical range is disclosed herein, the range is considered continuous and includes the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Furthermore, when the range refers to integers, it includes every integer between the minimum and maximum values ​​of the range. Additionally, when multiple ranges are provided to describe a feature or characteristic, the ranges may be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges to which they are incorporated.

[0030] Unless otherwise specified, all steps in this application may be performed sequentially or randomly. For example, the method comprising steps (a) and (b) indicates that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the mention that the method may also include step (c) indicates that step (c) may be added to the method in any order; for example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc. Unless otherwise stated, singular terms may include plural forms and should not be construed as having a quantity of one.

[0031] In this application, "above" or "below" includes the number itself. For example, "below 1" includes 1.

[0032] In this application, room temperature refers to 0~40℃, including but not limited to 10~40℃, or further to 20~30℃.

[0033] The present application will be further illustrated by the following examples, but these examples do not limit the scope of the present application.

[0034] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in this application, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. All reagents or instruments whose manufacturers are not specified are conventional products that can be purchased commercially. In addition to the specific methods, equipment, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description in this application, any prior art methods, equipment, and materials similar to or equivalent to those described, used, or made by the methods, equipment, and materials in the embodiments of this application may be used to implement this application.

[0035] Raw materials and reagents instructions In the following examples, the average degree of substitution of sulfobutyl-β-cyclodextrin is approximately 6.2-7.0; β-caryophyllene is naturally extracted with a purity ≥96%; potassium hydroxide is analytical grade in flake form; anhydrous ethanol is analytical grade; glycerol, magnesium stearate, and magnesium sulfate are all pharmaceutical grade; and dried Artemisia argyi is dried Artemisia argyi leaves with a moisture content ≤10%.

[0036] Example 1 The preparation method of the high-penetration moxibustion patch in this embodiment includes the following steps: 1) After crushing the dried mugwort, place it in a pulping machine, add solvent, and mix and pulp at a speed of 2500 prm to obtain a pulp; the mass ratio of dried mugwort to solvent is 1:1; the solvent is composed of deionized water and DMSO in a mass ratio of 1:0.005. 2) Add 250g of sulfobutyl-β-cyclodextrin to 2L of deionized water, then add an ethanol solution containing 5g of β-caryophyllene and mix well. Then add 50g of potassium hydroxide and stir for 30min to obtain an alkaline emulsion. Transfer the emulsion to a crystallization container for methanol vapor diffusion crystallization at a temperature of 25℃ for 60h. After crystallization, collect the crystals, wash with anhydrous ethanol, and dry to obtain the transdermal penetration enhancer. 3) Take 1kg of slurry, 30g of transdermal penetration promoter, 50g of glycerin, 20g of stearate, and 10g of magnesium sulfate, mix them evenly, and dry them at low temperature until the moisture content is less than 30% to obtain wet material. Then place the wet material in a shaping machine for shaping and dry it at low temperature with nitrogen blowing to obtain moxibustion tablets, controlling the moisture content to be less than 10%.

[0037] Example 2 The preparation method of the high-penetration moxibustion patch in this embodiment includes the following steps: 1) After crushing the dried mugwort, place it in a pulping machine, add solvent, and mix and pulp at a speed of 2500 prm to obtain a pulp; the mass ratio of dried mugwort to solvent is 1:1; the solvent is composed of deionized water and DMSO in a mass ratio of 1:0.005. 2) Add 200g of sulfobutyl-β-cyclodextrin to 2L of deionized water, then add an ethanol solution containing 5g of β-caryophyllene and mix well. Then add 40g of potassium hydroxide and stir for 30min to obtain an alkaline emulsion. Transfer the emulsion to a crystallization container for methanol vapor diffusion crystallization at a temperature of 25℃ for 60h. After crystallization, collect the crystals, wash with anhydrous ethanol, and dry to obtain the transdermal penetration enhancer. 3) Take 1kg of slurry, 30g of transdermal penetration promoter, 50g of glycerin, 20g of stearate, and 10g of magnesium sulfate, mix them evenly, and dry them at low temperature until the moisture content is less than 30% to obtain wet material. Then place the wet material in a shaping machine for shaping and dry it at low temperature with nitrogen blowing to obtain moxibustion tablets, controlling the moisture content to be less than 10%.

[0038] Example 3 The preparation method of the high-penetration moxibustion patch in this embodiment includes the following steps: 1) After crushing the dried mugwort, place it in a pulping machine, add solvent, and mix and pulp at a speed of 2500 prm to obtain a pulp; the mass ratio of dried mugwort to solvent is 1:1; the solvent is composed of deionized water and DMSO in a mass ratio of 1:0.005. 2) Add 300g of sulfobutyl-β-cyclodextrin to 2L of deionized water, then add an ethanol solution containing 5g of β-caryophyllene and mix well. Then add 60g of potassium hydroxide and stir for 30min to obtain an alkaline emulsion. Transfer the emulsion to a crystallization container for methanol vapor diffusion crystallization at a temperature of 25℃ for 60h. After crystallization, collect the crystals, wash with anhydrous ethanol, and dry to obtain the transdermal penetration enhancer. 3) Take 1kg of slurry, 30g of transdermal penetration promoter, 50g of glycerin, 20g of stearate, and 10g of magnesium sulfate, mix them evenly, and dry them at low temperature until the moisture content is less than 30% to obtain wet material. Then place the wet material in a shaping machine for shaping and dry it at low temperature with nitrogen blowing to obtain moxibustion tablets, controlling the moisture content to be less than 10%.

[0039] Control group 1 The preparation method of the moxibustion tablets in this control group includes the following steps: 1) After crushing the dried mugwort, place it in a pulping machine, add solvent, and mix and pulp at a speed of 2500 prm to obtain a pulp; the mass ratio of dried mugwort to solvent is 1:1; the solvent is composed of deionized water and DMSO in a mass ratio of 1:0.005. 2) Take 1kg of slurry, 50g of glycerin, 20g of stearate and 10g of magnesium sulfate and mix them evenly. Dry them at low temperature until the moisture content is less than 30% to obtain wet material. Then place the wet material in a shaping machine to shape it and dry it at low temperature with nitrogen blowing to obtain moxibustion tablets, controlling the moisture content to be less than 10%.

[0040] Control group 2 The preparation method of the moxibustion tablets in this control group includes the following steps: 1) After crushing the dried mugwort, place it in a pulping machine, add solvent, and mix and pulp at a speed of 2500 prm to obtain a pulp; the mass ratio of dried mugwort to solvent is 1:1; the solvent is composed of deionized water and DMSO in a mass ratio of 1:0.005. 2) Add 250g of β-cyclodextrin to 2L of deionized water, heat to 50℃, then add an ethanol solution containing 5g of β-caryophyllene and mix well. Stir for 2 hours, cool, let stand overnight at 4℃, filter, wash with water, dry at 40℃, and pulverize to obtain the transdermal penetration promoter. 3) Take 1kg of slurry, 30g of transdermal penetration promoter, 50g of glycerin, 20g of stearate, and 10g of magnesium sulfate, mix them evenly, and dry them at low temperature until the moisture content is less than 30% to obtain wet material. Then place the wet material in a shaping machine for shaping and dry it at low temperature with nitrogen blowing to obtain moxibustion tablets, controlling the moisture content to be less than 10%.

[0041] Performance testing 1. Take the transdermal penetration enhancers from Examples 1-3 and Control Group 2, with free β-caryophyllene as a control, and use a thermogravimetric analyzer to heat the samples from room temperature to 400℃ at a rate of 10℃ / min under a nitrogen atmosphere (flow rate 50mL / min). Record the initial weight loss temperature (the temperature corresponding to a cumulative weight loss of 5%), the maximum weight loss rate temperature, and the mass retention rate at 130℃ for 1h. The test results are shown in Table 1.

[0042] Table 1. Thermogravimetric analysis data of transdermal penetration enhancers in Examples 1-3 and Control Group 2. 2. A Franz vertical diffusion cell apparatus was used, with an effective diffusion area of ​​2.27 cm² and a receiving chamber volume of 15 mL. The receiving solution was a mixture of pH 7.4 phosphate buffer and anhydrous ethanol (volume ratio 4:1) to ensure proper diffusion conditions. The temperature of the receiving solution was precisely controlled at 37 ± 0.5 °C using a circulating water bath, and the magnetic stirrer was rotated at 300 rpm. The skin used for diffusion was extracted from the abdomen of healthy male SD rats (weighing 200 ± 20 g). After hair removal and removal of subcutaneous fat, intact and undamaged areas were selected for testing and equilibrated with physiological saline for 30 minutes before the experiment.

[0043] The moxibustion patches prepared in Examples 1-3 and Control Groups 1-2 were ground into uniform fine powder using a mortar and pestle, and then passed through an 80-mesh sieve for later use. 1.00 g of powder was accurately weighed and evenly spread on the surface of the stratum corneum of the skin in the supply pool. To simulate the heating conditions during actual use of the moxibustion patches, before the experiment began, the powders in each group were rapidly heated to 100°C on an infrared heating plate and held at that temperature for 5 minutes. They were then immediately transferred to the diffusion pool supply pool to begin timing, with the heating plate maintaining the temperature throughout the process. Samples of 1.0 mL were taken from the receiving chamber at 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h after the start of the experiment. An equal volume of fresh receiving liquid was immediately added after each sampling. After filtering the samples through a 0.45 μm microporous membrane, the concentrations of β-caryophyllene and eucalyptol were determined using gas chromatography-mass spectrometry in selected ion monitoring mode.

[0044] GC-MS analysis conditions: The chromatographic column was an HP-5MS flexible quartz capillary column, 30 m × 0.25 mm × 0.25 μm; the carrier gas was high-purity helium, with a flow rate of 1.0 mL / min; the injection port temperature was 250 °C; the temperature program was: initial 60 °C, held for 2 min, increased to 180 °C at 15 °C / min, then increased to 250 °C at 5 °C / min, held for 5 min; the split ratio was 10:1; the injection volume was 1 μL. Mass spectrometry conditions included an EI ion source with an electron energy of 70 eV, an ion source temperature of 230 °C, and a quadrupole temperature of 150 °C. Quantification was performed using the external standard method. The standard curves for β-caryophyllene and eucalyptol showed good linearity in the concentration range of 0.5–100 μg / mL (r > 0.999).

[0045] Data Calculation: Based on the drug concentration measured in the receiving solution at each sampling time point, the cumulative permeability per unit area Q (μg / cm²) is calculated using the following formula: Q = [C n ×V+∑(C i ×V s )] / A; In the formula, C n V represents the drug concentration in the receiving solution measured at the nth sampling point; V is the volume of the receiving chamber (15 mL); C i V represents the concentration at the i-th sampling point; sQ is the volume of each sample (1.0 mL); A is the effective diffusion area (2.27 cm²). Plotting Q against time t, the slope of the linear portion of the curve represents the steady-state permeation rate Js (μg·cm⁻¹). -2 ·h -1 The cumulative permeability (Q24) and steady-state permeability (Js) over 24 hours are shown in Table 2.

[0046] Table 1. Transdermal absorption test data of moxibustion tablets in Examples 1-3 and Control Group 2 Analysis of the data in Table 2 shows that the cumulative 24-hour permeation of eucalyptol in control group 1 was only 89.7 μg / cm², indicating limited transdermal efficiency of the active ingredients in Artemisia argyi. In control group 2, after using a β-CD physical inclusion complex to provide β-caryophyllene, the Q24 of eucalyptol increased to 142.6 μg / cm², with a permeation enhancement ratio of 1.59, confirming that β-caryophyllene can indeed promote the transdermal absorption of the active ingredients in Artemisia argyi. However, the Q24 of β-caryophyllene itself was only 92.4 μg / cm², and the transdermal release rate significantly decreased, indicating insufficient thermal protection of the physical inclusion complex. Some β-caryophyllene was degraded or volatilized during the 100℃ pretreatment stage, resulting in insufficient subsequent permeation-enhancing motive force.

[0047] In comparison, the β-caryophyllene Q24 in Example 1 of this application reached 186.5 μg / cm², which is approximately 2.02 times that of Control Group 2, and the penetration enhancement ratio for eucalyptol reached 2.70, which is approximately 1.70 times that of Control Group 2. It can be seen that the release rate of β-caryophyllene in Example 1 remained relatively stable within 0–24 hours, without significant rate decay. This result fully confirms that the thermally stable crystal framework formed by K⁺ bridging of sulfobutyl-β-cyclodextrin effectively encapsulates and protects β-caryophyllene, enabling its continuous release in a controlled manner. This maintains the perturbation state of stratum corneum lipids throughout the transdermal cycle, providing a continuous and efficient penetration-enhancing drive for the active ingredients of Artemisia argyi.

[0048] Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A method for preparing a high-permeability moxibustion patch, characterized in that: Includes the following steps: 1) Crush dried Artemisia argyi into powder, mix with solvent and slurry to obtain slurry; the solvent is composed of deionized water and dimethyl sulfoxide; 2) Dissolve sulfobutyl-β-cyclodextrin in deionized water, add an alcohol solution containing β-caryophyllene and mix well, then add potassium hydroxide and stir to form an alkaline emulsion; allow the alkaline emulsion to contact methanol vapor for vapor diffusion crystallization, collect the crystals after crystallization, wash and dry to obtain a transdermal penetration enhancer. 3) Mix the slurry, transdermal penetration enhancer, and pharmaceutically acceptable excipients evenly, dry at low temperature to obtain wet material, and then dry the wet material under low temperature nitrogen blowing to obtain the final product.

2. The method for preparing the high-penetration moxibustion patch according to claim 1, characterized in that: The mass ratio of deionized water to dimethyl sulfoxide in the solvent is 1:(0.003-0.01).

3. The method for preparing the high-penetration moxibustion patch according to claim 1, characterized in that: The ratio of sulfobutyl-β-cyclodextrin to water is (50-150) g: 1 L.

4. The method for preparing the high-penetration moxibustion patch according to claim 1, characterized in that: The mass ratio of β-caryophyllene to sulfobutyl-β-cyclodextrin is 1:(30-80).

5. The method for preparing the high-penetration moxibustion patch according to claim 1, characterized in that: The mass ratio of potassium hydroxide to sulfobutyl-β-cyclodextrin is 1:(3-8).

6. The method for preparing the high-penetration moxibustion patch according to claim 1, characterized in that: The temperature for vapor diffusion crystallization is 20-30℃, and the time is 48-72 seconds.

7. The method for preparing the high-penetration moxibustion patch according to claim 1, characterized in that: The pharmaceutically acceptable excipients are selected from at least one of wetting agents, surfactants, and inorganic salts.

8. The method for preparing the high-penetration moxibustion patch according to claim 7, characterized in that: The wetting agent is glycerol, the surfactant is stearate, and the inorganic salt is magnesium sulfate.

9. A high-penetration moxibustion patch, characterized in that: It is prepared by any one of the preparation methods described in claims 1-8.

10. An application of a high-penetration moxibustion patch, characterized in that: The application of the moxibustion patch prepared by any one of the preparation methods described in claims 1-8 in traditional Chinese medicine moxibustion products, wherein the traditional Chinese medicine moxibustion products include moxibustion patches or self-heating moxibustion patches.

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