A preparation method of a traditional Chinese medicine compound granule for treating wind-dryness damaging lung pattern

Abstract

This invention relates to the field of traditional Chinese medicine pharmaceutical engineering technology, and discloses a method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury syndrome. Using *Sedum spectabile*, *Aster tataricus*, and *Tussilago farfara* as raw materials, *Aster tataricus* and *Tussilago farfara* are extracted using a specific molar ratio of levamisole-lactic acid deep eutectic solvent combined with an alternating pulsed supercritical pressure field to obtain a lipid-soluble microemulsion core substrate. The ethanol extract of *Sedum spectabile* is purified sequentially by ultrafiltration and polyamide resin, concentrated, and then complexed with cationic chitosan to obtain a flavonoid-chitosan refined extract outer shell substrate. Finally, the granules are self-assembled by coaxial dual-channel atomization in a fluidized bed to obtain a granule product with a double-layer physically cross-linked microcapsule structure. This invention eliminates ineffective hygroscopic impurities, reduces the dry extract rate and excipient dosage, effectively blocks the oxidative volatilization of lipid-soluble components, forces heterogeneous pharmacodynamic components to achieve high-synchronous and synchronous release, and improves the clinical efficacy of non-addictive antitussive and expectorant effects.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine pharmaceutical engineering technology, and in particular to a method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury syndrome. Background Technology

[0002] Cough and sputum are the most common clinical manifestations of respiratory diseases, with wind-dryness injuring the lungs being particularly prevalent. Currently, most expectorant and antitussive products used clinically contain ephedra and codeine, posing significant risks of addiction and limiting their clinical use. In traditional Chinese medicine compound preparations, those without toxic or controlled substances often have numerous ingredients in their prescriptions, leading to significant difficulties in quality control during the production process.

[0003] There is a traditional folk remedy for coughs, with a concise prescription consisting of only three herbs: *Sedum spectabile* (principal herb), *Aster tataricus* (assistant herb), and *Tussilago farfara* (auxiliary herb). It is primarily used to treat coughs caused by wind-dryness damaging the lungs. Traditionally, this remedy is prepared by decocting the herbs in water. However, to make it easier for patients to take, conventional methods often concentrate the decoction and add dextrin and sucrose to create granules. However, this traditional preparation process has insurmountable technical defects: First, the core active substances in Aster tataricus and Tussilago farfara (such as asterone and tuftolone) are mostly fat-soluble components. Traditional high-temperature decoction not only has an extremely low extraction rate, but also easily leads to the oxidative degradation of volatile components. Second, the decoction process will extract a large amount of ineffective polysaccharides, starch and mucilage from the medicinal materials, resulting in an abnormally high dry extract rate (about 30%) and easy hygroscopicity. This means that the final preparation must add an excessive amount of excipients, resulting in an excessively large single dose, which seriously reduces the medication compliance of patients with sensitive respiratory mucosa. Finally, traditional physical mixing and granulation cannot solve the problem of synchronous release of the principal drug (water-insoluble flavonoids) and the adjuvant drugs (fat-soluble volatiles) in the gastrointestinal tract, resulting in obvious temporal and spatial asynchrony of drug efficacy. Summary of the Invention

[0004] This invention provides a method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury syndrome. By constructing a core-shell double-layer microcapsule physical cross-linking structure, it solves the process problems of high dry paste rate and easy volatility and oxidation of effective ingredients in traditional Chinese medicine granules, and realizes the targeted synchronous release and nonlinear synergistic effect of multi-component pharmacological substances.

[0005] This invention provides a method for preparing a compound Chinese medicine granule for treating wind-dryness-induced lung injury syndrome. The method comprises weighing 500 parts by weight of *Sedum morganianum*, 333 parts by weight of *Aster tataricus*, and 167 parts by weight of *Tussilago farfara* as raw materials. The preparation method includes the following steps:

[0006] (1) Mix L-menthol and natural lactic acid in a molar ratio of 1:2.35 to 1:2.45 and heat and stir to prepare a deep eutectic solvent;

[0007] (2) After crushing Aster tataricus and Tussilago farfara, place them in a supercritical extraction vessel, introduce supercritical carbon dioxide fluid and the deep eutectic solvent, and perform extraction by superimposing an alternating pulse pressure field with a frequency of 15 Hz and an amplitude of ±4.5 MPa on the basic extraction pressure of 18 MPa. The extraction fluid is depressurized and released through a desorption vessel to obtain a lipid-soluble microemulsion.

[0008] (3) The stone plant was subjected to dynamic countercurrent ethanol extraction, the extract was collected, the supernatant after centrifugation of the extract was treated by an ultrafiltration membrane system, the permeate was collected, the permeate was passed through a polyamide resin column, and after elution with pure water, it was eluted with ethanol and the ethanol eluent was collected.

[0009] (4) Determine the total flavonoid content in the ethanol eluent, add cationic chitosan with a degree of deacetylation of 83% to 87% to the ethanol eluent, control the mass ratio of total flavonoids to cationic chitosan in the ethanol eluent to be 1:0.6, concentrate under vacuum to obtain flavonoid-chitosan refined extract.

[0010] (5) Place microcrystalline cellulose in a fluidized bed, set the inlet air temperature to 42°C to make it fluidized, use a coaxial dual-channel atomizing nozzle to input the lipid-soluble microemulsion into the inner channel and the flavonoid-chitosan refined extract into the outer channel, control the volume flow rate ratio of the inner channel to the outer channel to be 1:4.5, spray into the fluidized bed to coat the surface of the microcrystalline cellulose, dry and shape to obtain the traditional Chinese medicine compound granules with a double-layer microcapsule structure with the lipid-soluble microemulsion as the core and the flavonoid-chitosan refined extract as the outer shell.

[0011] Furthermore, in step (1), the heating and stirring temperature for obtaining the deep eutectic solvent is 60°C to 70°C, and the stirring time is 40 minutes to 60 minutes.

[0012] Furthermore, in step (2), the extraction temperature is controlled at 40°C to 45°C, and the amount of the deep eutectic solvent introduced is 1.2 to 1.5 times the total mass of the aster and the coltsfoot flower.

[0013] Furthermore, in step (3), the operating parameters for the dynamic countercurrent ethanol extraction of the *Sedum morganianum* are as follows:

[0014] An ethanol aqueous solution with a volume percentage concentration of 70% was used as the extraction solvent. The amount of ethanol aqueous solution added was 6 to 8 times the mass of the stone orchid. Dynamic countercurrent extraction was performed twice, with each extraction time being 1 to 1.5 hours.

[0015] Furthermore, in step (3), when the supernatant after centrifugation of the extract is passed through an ultrafiltration membrane system, the molecular weight cutoff of the ultrafiltration membrane system is 10,000 Da to 30,000 Da.

[0016] Furthermore, in step (3), the pure water elution volume of the polyamide resin column is 4 column volumes;

[0017] The operating parameters for centralized elution with ethanol were as follows: using ethanol with a volume percentage concentration of 80%, eluting 5 column volumes at a flow rate of 1.5 times column volumes / hour.

[0018] Furthermore, in step (4), the operating parameters for vacuum concentration are: concentration temperature not exceeding 60℃, and vacuum degree from -0.08MPa to -0.09MPa.

[0019] Furthermore, in step (5), the drying and shaping process involves continuously drying in the fluidized bed until the particle moisture content drops below 3% and then the fluidization is stopped.

[0020] The present invention also provides a traditional Chinese medicine compound granule for wind-dryness-induced lung injury syndrome prepared according to the preparation method described above. The traditional Chinese medicine compound granule includes a microcrystalline cellulose core and a double-layer microcapsule structure covering the surface of the microcrystalline cellulose core. The double-layer microcapsule structure has a lipophilic core composed of Aster tataricus extract, Tussilago farfara extract and deep eutectic solvent, and an outer shell composed of Dendrobium nobile extract and cationic chitosan.

[0021] The beneficial effects of this invention are as follows:

[0022] This invention utilizes a specific molar ratio of eutectic solvent (DES) combined with alternating pulsed supercritical fluid extraction technology, along with polyamide resin purification and coaxial dual-channel electrostatic self-assembly molding process, to construct a bilayer physically cross-linked microcapsule structure at the microscopic level. This structure consists of a lipid-soluble volatile core and a flavonoid-chitosan shell. This structure not only eliminates ineffective impurities that cause high hygroscopicity, reducing the dry powder rate and the amount of excipients required per dose, but also significantly improves the physical stability of the particles by blocking the oxidation and volatilization of lipid-soluble components such as asterone through the dense shell. Simultaneously, this microstructure forces volatile components with significantly different solubilities and poorly soluble flavonoids to achieve synchronous, co-frequency release at the target organ, shortening the onset time of cough suppression and reducing the effective dose, thus achieving a non-linear synergistic effect of the principal and adjuvant drugs in both spatial and temporal dimensions. Attached Figure Description

[0023] Figure 1 This is a flowchart illustrating the preparation method of the traditional Chinese medicine compound granules for wind-dryness-induced lung injury syndrome according to the present invention.

[0024] Figure 2 This is a schematic cross-sectional view of the physical cross-linking structure of the double-layer microcapsule of the traditional Chinese medicine compound granules of the present invention.

[0025] Figure 3 This is a comparison of pharmacokinetic (PK) blood drug concentration-time curves in rats in Experiment Example 2 of this invention.

[0026] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments and experimental examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0028] Example 1: Optimal preparation of compound Chinese medicine granules

[0029] This embodiment provides a method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury syndrome, such as... Figure 1 As shown, the first step is to prepare the raw materials. Weigh out 500g of *Sedum morganianum*, 333g of *Aster tataricus*, and 167g of *Tussilago farfara*, all according to the Chinese Pharmacopoeia standards. This formula has the effects of moistening the lungs, lowering qi, resolving phlegm, and relieving cough, and is mainly used to treat cough due to wind-dryness damaging the lungs. The specific preparation steps are as follows:

[0030] (1) Preparation of DES entrainer: L-menthol and natural lactic acid were mixed at a molar ratio of 1:2.40 and placed in a heat-collecting magnetic stirrer. The temperature was set to 65°C and the mixture was heated and stirred for 50 minutes until a transparent homogeneous liquid was formed, thus obtaining deep eutectic solvent (DES).

[0031] (2) Extraction of Aster tataricus and Coltsfoot (construction of a lipophilic core): Aster tataricus and Coltsfoot were pulverized to 40 mesh, mixed evenly, and then loaded into a supercritical extraction vessel. Supercritical carbon dioxide fluid was introduced (the carbon dioxide flow rate was set to 25 L / h), and the above-mentioned deep eutectic solvent was pumped in (the amount introduced was 1.3 times the total mass of Aster tataricus and Coltsfoot). The extraction temperature was set to 42℃, the basic extraction pressure was set to 18 MPa, and an alternating pulse pressure field with a frequency of 15 Hz and an amplitude of ±4.5 MPa was superimposed on it for dynamic extraction for 1.5 hours. After the extraction fluid was depressurized and degassed in a desorption vessel (the specific desorption parameters were: the first-stage desorption pressure was controlled at 8 MPa and the temperature at 50℃ to remove heavy component impurities; then it entered the second-stage desorption vessel, where the desorption pressure was controlled at 4 MPa and the temperature at 40℃ for depressurization and degassing), and a lipophilic microemulsion rich in asterone and coltsfootone was collected.

[0032] (3) Extraction and purification of *Sedum spectabile* (construction of hydrophilic shell matrix): *Sedum spectabile* was cut into segments and extracted twice using a 70% (v / v) ethanol aqueous solution as the extraction solvent (the amount added was 7 times the mass of *Sedum spectabile*), each time for 1.2 hours. The extracts were combined and centrifuged in a tubular centrifuge (centrifugation speed set at 12000 r / min, centrifugation time for 15 minutes). The supernatant was taken and passed through an ultrafiltration membrane system with a molecular weight cutoff of 20000 Da to remove macromolecular polysaccharides; the permeate (in separation engineering terminology, the permeate of the ultrafiltration system) was then loaded onto a polyamide resin column (using 30-60 mesh polyamide resin), first eluted with 4 column volumes of purified water to remove impurities, and then concentratedly eluted with 80% (v / v) ethanol at a flow rate of 1.5 times the column volume / hour for 5 column volumes, and the ethanol eluent was collected.

[0033] (4) Polymer Complexation and Concentration: The total flavonoid content in the ethanol eluent was determined by high performance liquid chromatography (HPLC) (the determination method was specified as follows: using ≥98% purity of physalisin as a reference standard, employing an octadecylsilane-bonded silica C18 column, using methanol-0.1% phosphoric acid aqueous solution as the mobile phase for gradient elution, setting the detection wavelength to 340 nm, and calculating the total flavonoid concentration using the external standard method). Cationic chitosan with a degree of deacetylation of 85% was added, and the mass ratio of total flavonoids to cationic chitosan was precisely controlled at 1:0.6. The mixture was concentrated under reduced pressure at 55℃ and a vacuum of -0.085 MPa to obtain a refined flavonoid-chitosan extract.

[0034] (5) Self-assembly molding: A suitable amount of microcrystalline cellulose was placed in a multi-effect fluidized bed as the starting nucleus, and the inlet air temperature was set to 42℃ to achieve a fluidized state. A coaxial dual-channel atomizing nozzle (with the atomizing air pressure set to 0.15MPa) was used to input the above-mentioned lipid-soluble microemulsion into the inner channel and the above-mentioned flavonoid-chitosan refined extract into the outer channel. The volume ratio of the inner channel flow rate to the outer channel flow rate was controlled to be 1:4.5. Under high-pressure airflow shearing, the two fluids were injected into the fluidized bed, and an electrostatic self-assembly phase transition occurred instantaneously on the surface of the microcrystalline cellulose. Continuous fluidized drying was performed until the particle moisture content dropped to 2.5%, yielding traditional Chinese medicine compound granules. Figure 2 As shown, the particle has a double-layer microcapsule physical cross-linking structure with microcrystalline cellulose as the base, a lipid-soluble microemulsion as the core, and flavonoid-chitosan as the outer shell.

[0035] Example 2: The raw materials are 500g of *Gynostemma pentaphyllum*, 333g of *Aster tataricus*, and 167g of *Colletotrichum candida*.

[0036] (1) Preparation of DES entrainer: L-menthol and natural lactic acid were mixed at a molar ratio of 1:2.35 and heated and stirred at 60°C for 40 minutes.

[0037] (2) Extraction: Extraction temperature 40℃, basic extraction pressure 18MPa, superimposed with 15Hz / ±4.5MPa alternating pulse, carbon dioxide flow rate 20L / h, DES injection rate 1.2 times the amount of medicinal material. Analysis parameters: first-stage analysis pressure 9MPa, temperature 45℃; second-stage analysis pressure 5MPa, temperature 35℃.

[0038] (3) Extraction and purification: The amount of ethanol-water solution used was 6 times, and the countercurrent extraction was carried out for 1 hour each time; the centrifugation speed was 10000r / min, and the centrifugation time was 10 minutes; the molecular weight cutoff of the ultrafiltration membrane was 10000Da; the polyamide resin (30-60 mesh) was eluted with 80% ethanol.

[0039] (4) Polymer complexation and concentration: The total flavonoids were determined according to the aforementioned HPLC external standard method. Cationic chitosan with a deacetylation degree of 83% was selected and the mass ratio was controlled at 1:0.6. It was concentrated at 60℃ and -0.08MPa.

[0040] (5) Self-assembly molding: fluidized bed inlet air temperature 42℃, atomizing air pressure 0.12MPa, coaxial spray internal and external flow velocity ratio 1:4.5, dried to moisture content 2.8%.

[0041] Example 3: The raw materials are 500g of *Gynostemma pentaphyllum*, 333g of *Aster tataricus*, and 167g of *Colletotrichum candida*.

[0042] (1) Preparation of DES entrainer: L-menthol and natural lactic acid were mixed at a molar ratio of 1:2.45 and heated and stirred at 70°C for 60 minutes.

[0043] (2) Extraction: Extraction temperature 45℃, base pressure 18MPa, superimposed with 15Hz / ±4.5MPa alternating pulses, carbon dioxide flow rate 30L / h, DES injection rate 1.5 times the amount of medicinal material. Analysis parameters: first-stage analysis pressure 7MPa, temperature 55℃; second-stage analysis pressure 3MPa, temperature 45℃.

[0044] (3) Extraction and purification: The amount of ethanol-water solution used was 8 times, and the countercurrent extraction was carried out for 1.5 hours each time; the centrifugation speed was 15000r / min, and the centrifugation time was 20 minutes; the molecular weight cutoff of the ultrafiltration membrane was 30000Da; the elution parameters of polyamide resin (30-60 mesh) were the same as in Example 1.

[0045] (4) Polymer complexation and concentration: The total flavonoids were determined according to the aforementioned HPLC external standard method. Cationic chitosan with a deacetylation degree of 87% was selected and the mass ratio was controlled at 1:0.6. It was concentrated at 50℃ and -0.09MPa.

[0046] (5) Self-assembly molding: fluidized bed inlet air temperature 42℃, atomizing air pressure 0.18MPa, coaxial spray internal and external flow velocity ratio 1:4.5, dried to moisture content 2.1%.

[0047] Comparative Example 1 (Traditional water decoction and granulation process)

[0048] Preparation using existing technology: Mix 500g of *Sedum morganianum*, 333g of *Aster tataricus*, and 167g of *Colletotrichum candida*, add water and decoct twice, combine the decoctions, concentrate to a thick paste, add dextrin and sucrose as excipients, physically mix and granulate using a swing granulator, and dry to obtain the final product.

[0049] Comparative Example 2 (Conventional Physical Process)

[0050] The volatile oils of Aster tataricus and Coltsfoot were extracted using conventional supercritical carbon dioxide extraction (without specific DES, no pulsed pressure field, constant extraction pressure of 25 MPa, extraction temperature of 45 °C, carbon dioxide flow rate of 25 L / h, and single-stage desorption at 6 MPa and 40 °C after 2 hours of extraction). The extract of Lithops was directly concentrated (without ultrafiltration and resin purification, concentrated to a thick paste with a relative density of 1.15 at 60 °C and -0.08 MPa). The two extracts were mixed with dextrin (the amount of dextrin added was 1.2 times the total mass of the thick paste and volatile oil) and then subjected to conventional fluidized bed top spray granulation and drying (without coaxial spraying and a specific polymer matrix, the inlet air temperature was set to the conventional 55 °C, and the top spraying pressure was 0.15 MPa).

[0051] Experimental Example 1: Multidimensional Microscopic Characterization Experiment (Confirmation of the Bilayer Microcapsule Structure of the Target Product)

[0052] To prove that the compound granules prepared in Example 1 of this invention truly contain a "double-layer microcapsule structure with a lipid-soluble microemulsion as the core and a flavonoid-chitosan refined extract as the outer shell", multidimensional characterization technology was used for verification. The specific test results are shown in Table 1.

[0053] Table 1: Summary of Multidimensional Microscopic Characterization Results of Compound Traditional Chinese Medicine Granules

[0054] Characterization test items Detection object Core measured data and spectral performance Physical structure confirmation conclusions FIB-SEM analysis Particle physical cross section The three-layer interface exhibits a clear contrast difference: an inner microcrystalline cellulose substrate, a middle dense ring (1.5-2.0 μm thick), and an outer rough network coating layer. It was confirmed that there is a multi-layered core-shell morphology, rather than a single-layered homogeneous structure. TOF-SIMS analysis Particle-cut molecular fragments Menthol and asterone characteristic fragments were tightly enriched in the middle ring; chitosan and physalisin characteristic fragments were enriched in the outermost ring. The spatial arrangement confirms that a tight "core-shell" chemical composition isolation has been achieved. Zeta potential monitoring Pre-spray granulation fluid The fluid potential in the inner channel is -18.4 mV; the fluid potential in the outer channel is +41.2 mV. The potential jumps and stabilizes at +19.6 mV the instant the two fluids merge. It was confirmed that a violent electrostatic self-assembly phase transition occurred between two matrices with opposite charges. DSC thermodynamic analysis Granular products and individual monomers The sharp endothermic melting peak of pure asterone at approximately 68°C was significantly shifted (to 82°C) in the compound particle spectrum, and the enthalpy change was greatly reduced. This demonstrates that the volatile active ingredients are tightly physically bound by the outer structure.

[0055] Experiment Example 2: Verification of Technical Effects

[0056] 1. High temperature and high humidity accelerate stability

[0057] The particles from Example 1, Comparative Example 1, and Comparative Example 2 were placed in a constant temperature and humidity chamber (40℃ / RH75%) and left open for 6 months. The core stability index was tested, and the results are shown in Table 2.

[0058] Table 2: Comparison Results of Accelerated Stability under High Temperature and High Humidity

[0059] Grouping Initial dry extract yield (per 100g of raw medicinal material) Asterone retention rate after 6 months Critical relative humidity (CRH) Core evaluation conclusions Comparative Example 1 31.5g 15.6% 61% It has an extremely high drying rate, is highly hygroscopic, and oxidizes rapidly. Comparative Example 2 12.3g 34.2% 72% The dry paste yield decreased, but volatilization and degradation remained severe. Example 1 9.8g 91.5% 84% Significantly reduces dry paste yield and blocks oxidation and volatilization.

[0060] Conclusion: The specific process of this invention solves the problem of high dry extract rate in traditional decoction method, while the robust physical microcapsules block the oxidation and volatilization of fat-soluble components, achieving unexpected stability.

[0061] 2. Synergistic sustained release and pharmacokinetics (PK)

[0062] Using a rat gavage model, the time to peak concentration of the effective components in the blood was measured. The comparison of the onset time and median effective dose (ED50) of ammonia-induced cough suppression with changes in plasma drug concentration over time is as follows: Figure 3 As shown, the specific data results are shown in Table 3.

[0063] Table 3: Comparison of Pharmacokinetics and Antitussive Pharmacodynamics

[0064] Grouping Asterone (h) Stone Plant Extract #imgpt2#(h) Cough suppressant onset time (min) #imgpt3#(g / kg) Drug release characteristic evaluation Comparative Example 1 0.8 2.5 24 4.5 Release is severely asynchronous, onset of action is slow, and large doses are required. Comparative Example 2 1.0 2.2 19 3.2 There is a significant time lag and weak coordination. Example 1 2.8 3.0 8 0.8 Synchronized and synchronized release, extremely rapid effect

[0065] Conclusion: The microcapsule structure of this invention forces the lipid-soluble (asterone) and water-soluble (styrax) components, which originally had significantly different solubilities, to achieve synchronous and co-frequency release at the target site, greatly shortening the onset time of cough suppression and reducing #imgpt4# to a low level. The synergistic effect of the principal, assistant, and adjuvant drugs in physical space brings about a non-linear improvement in efficacy, which significantly exceeds the reasonable expectations of those skilled in the art for conventional process combinations.

[0066] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, apparatus, article, or method that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, apparatus, article, or method. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, apparatus, article, or method that includes that element.

[0067] The above description is merely a preferred embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural or procedural transformations made based on the content of the present invention's specification and drawings, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A preparation method of a traditional Chinese medicine compound granule for wind-dryness damaging lung syndrome, characterized in that, Based on mass parts, 500 parts of *Sedum morganianum*, 333 parts of *Aster tataricus*, and 167 parts of *Colletotrichum candida* were weighed as raw materials. The preparation method includes the following steps: (1) Mix L-menthol and natural lactic acid in a molar ratio of 1:2.35 to 1:2.45 and heat and stir to prepare a deep eutectic solvent; (2) After crushing Aster tataricus and Tussilago farfara, place them in a supercritical extraction vessel, introduce supercritical carbon dioxide fluid and the deep eutectic solvent, and perform extraction by superimposing an alternating pulse pressure field with a frequency of 15 Hz and an amplitude of ±4.5 MPa on the basic extraction pressure of 18 MPa. The extraction fluid is depressurized and released through a desorption vessel to obtain a lipid-soluble microemulsion. (3) The stone plant was subjected to dynamic countercurrent ethanol extraction, the extract was collected, the supernatant after centrifugation of the extract was treated by an ultrafiltration membrane system, the permeate was collected, the permeate was passed through a polyamide resin column, and after elution with pure water, it was eluted with ethanol and the ethanol eluent was collected. (4) Determine the total flavonoid content in the ethanol eluent, add cationic chitosan with a degree of deacetylation of 83% to 87% to the ethanol eluent, control the mass ratio of total flavonoids to cationic chitosan in the ethanol eluent to be 1:0.6, concentrate under vacuum to obtain flavonoid-chitosan refined extract. (5) Place microcrystalline cellulose in a fluidized bed, set the inlet air temperature to 42°C to make it fluidized, use a coaxial dual-channel atomizing nozzle to input the lipid-soluble microemulsion into the inner channel and the flavonoid-chitosan refined extract into the outer channel, control the volume flow rate ratio of the inner channel to the outer channel to be 1:4.5, spray into the fluidized bed to coat the surface of the microcrystalline cellulose, dry and shape to obtain the traditional Chinese medicine compound granules with a double-layer microcapsule structure with the lipid-soluble microemulsion as the core and the flavonoid-chitosan refined extract as the outer shell.

2. The method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury according to claim 1, characterized in that, In step (1), the heating and stirring temperature for obtaining the deep eutectic solvent is 60°C to 70°C, and the stirring time is 40 minutes to 60 minutes.

3. The method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury according to claim 1, characterized in that, In step (2), the extraction temperature is controlled at 40°C to 45°C, and the amount of the deep eutectic solvent introduced is 1.2 to 1.5 times the total mass of the aster and the coltsfoot flower.

4. The method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury according to claim 1, characterized in that, In step (3), the operating parameters for the dynamic countercurrent ethanol extraction of the *Sedum morganianum* are as follows: An ethanol aqueous solution with a volume percentage concentration of 70% was used as the extraction solvent. The amount of ethanol aqueous solution added was 6 to 8 times the mass of the stone orchid. Dynamic countercurrent extraction was performed twice, with each extraction time being 1 to 1.5 hours.

5. The method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury according to claim 1, characterized in that, In step (3), when the supernatant after centrifugation of the extract is passed through an ultrafiltration membrane system, the molecular weight cutoff of the ultrafiltration membrane system is 10,000 Da to 30,000 Da.

6. The method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury according to claim 1, characterized in that, In step (3), the pure water elution volume of the polyamide resin column is 4 column volumes; The operating parameters for centralized elution with ethanol were as follows: using ethanol with a volume percentage concentration of 80%, eluting 5 column volumes at a flow rate of 1.5 times column volumes / hour.

7. The method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury according to claim 1, characterized in that, In step (4), the operating parameters for vacuum concentration are: concentration temperature not exceeding 60℃, and vacuum degree from -0.08MPa to -0.09MPa.

8. The method for preparing compound granules of traditional Chinese medicine for wind-dryness-induced lung injury according to claim 1, characterized in that, In step (5), drying and shaping is performed by continuously drying in the fluidized bed until the particle moisture content drops below 3% and then fluidization is stopped.

9. A traditional Chinese medicine compound granule for treating wind-dryness-induced lung injury syndrome prepared by the preparation method according to any one of claims 1 to 8, characterized in that, The traditional Chinese medicine compound granules include a microcrystalline cellulose core and a double-layer microcapsule structure covering the surface of the microcrystalline cellulose core. The double-layer microcapsule structure has a lipophilic core composed of Aster tataricus extract, Tussilago farfara extract and a deep eutectic solvent, and an outer shell composed of Dendrocalamus oleracea extract and cationic chitosan.

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