Traditional Chinese medicine composition for treating asthma in non-acute attack stage and preparation method of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating asthma in a non-acute attack stage and a preparation method thereof, and belongs to the field of traditional Chinese medicine compositions. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: cassia twig, poria cocos, peach kernel, radix paeoniae rubra, moutan bark, ginger, Chinese date, honey-fried licorice root, magnolia flower and cocklebur fruit. According to the traditional Chinese medicine composition, traditional Chinese medicine differentiation and a modern pathological mechanism are combined, a treatment scheme which is accurate in formula, clear in mechanism, exact in curative effect and high in safety is provided, and multi-target intervention is carried out aiming at the complex pathological state of the lung deficiency fluid retention and blood stasis syndrome in the non-acute attack period of asthma; the problems that existing traditional Chinese medicine compound syndromes are incomplete in coverage, western medicine treatment is large in side effect, single in mechanism and the like are effectively solved, and a new choice is provided for clinical treatment of the asthma in the non-acute attack stage (the syndrome of lung deficiency, fluid retention and blood stasis).

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine compositions, and in particular to a traditional Chinese medicine composition for treating non-acute exacerbations of asthma and its preparation method. Background Technology

[0002] Bronchial asthma is a heterogeneous disease characterized by chronic airway inflammation, hyperresponsiveness, and reversible airflow limitation. Clinically, asthma is divided into acute exacerbation phases and non-acute exacerbation phases (remission phases). During non-acute exacerbation phases, patients do not experience severe acute symptoms, but airway inflammation persists, accompanied by discomfort such as cough, sputum production, chest tightness, and decreased exercise tolerance. They are also prone to acute exacerbations triggered by allergens, infections, cold, and other factors. Frequent exacerbations accelerate airway remodeling, leading to a progressive decline in lung function and severely impacting patients' quality of life. Therefore, effective intervention during non-acute exacerbation phases to reduce acute exacerbations and slow disease progression is crucial for comprehensive asthma management.

[0003] Modern medicine primarily treats asthma during non-acute exacerbations with long-term medications, focusing on suppressing airway inflammation and reducing airway hyperresponsiveness. Key approaches include inhaled corticosteroids (ICS), combinations of ICS and long-acting β2-agonists (ICS / LABA), leukotriene receptor antagonists (LTRA), and targeted biologics (such as anti-IgE and anti-IL-5 monoclonal antibodies). These therapies have shown some effectiveness in controlling symptoms and improving lung function. However, existing Western medicine approaches still have significant limitations: long-term use of ICS may lead to oropharyngeal candidiasis, hoarseness, and potentially affect bone density and blood sugar; targeted biologics are expensive and have a narrow applicable population; current treatments mainly focus on suppressing type II inflammation, and are insufficient in addressing "neuro-immune interaction disorders" (such as increased vagal tone and imbalance in neurogenic inflammatory regulation), failing to fundamentally reverse airway sensitization; in addition, Western medicine approaches are mostly "symptomatic treatments," with limited effectiveness in improving patients' overall symptoms related to TCM syndromes (such as fatigue and aversion to cold), regulating constitution, and enhancing "vital energy," and cannot effectively manage nasal symptoms (allergic rhinitis) that often coexist with asthma, thus cutting off the important trigger of "naso-pulmonary reflex."

[0004] Traditional Chinese medicine (TCM) classifies asthma as the category of "wheezing disorder" and believes that the core pathogenesis during the non-acute attack period lies in "deficiency in origin and excess in superficiality". The deficiency in origin is mainly manifested by qi deficiency of the lung, spleen, and kidney; the excess in superficiality is mainly characterized by latent phlegm in the lung and blood stasis caused by prolonged illness invading the collaterals. Previous clinical studies have shown that among patients with asthma during the non-acute attack period, the complex syndrome type of "qi deficiency of the lung, retention of fluid, and blood stasis" accounts for as high as 68.3%, becoming the key and difficult points for clinical intervention. Patients with this syndrome type often present with cough, expectoration of clear and thin frothy sputum, chest distress or stabbing pain, aversion to cold, shortness of breath and weakness, dark lips and nails, pale and dull tongue, white and slippery tongue coating, and string-taut, slippery or unsmooth pulse. The key to its pathogenesis lies in the deficiency of lung qi, the weakness of the exterior defense, the accumulation of body fluids into retained fluid; the lack of qi propulsion ability, combined with the stagnation of cold fluid, resulting in poor blood circulation and the generation of internal blood stasis; the mutual binding of fluid and stasis, blocking the lung collaterals, forming a vicious cycle. At the same time, due to the lack of nourishment of the nasal cavity due to lung qi deficiency, it is vulnerable to external pathogens, and the sensitized state of the nasal mucosa can induce or exacerbate airway reactions through the "nose-lung reflex".

[0005] Currently, traditional Chinese medicine is widely used in the treatment of asthma during the non-acute attack period. Classical prescriptions such as Guizhi Fuling Pills (Ramulus Cinnamomi, Poria, Semen Persicae, Radix Paeoniae Rubra, Cortex Moutan) have the effects of warming the meridians, promoting blood circulation to remove blood stasis, and promoting diuresis to excrete dampness. Existing studies have applied it to the treatment of asthma, mainly targeting the pathogenesis of "blood stasis". However, the original prescription focuses on "removing blood stasis" and partially "resolving retained fluid", lacking specific tonifying drugs for "lung qi deficiency" in the formula, and also lacking components for strongly warming and resolving cold fluid and dredging the nasal passages and desensitizing. Therefore, directly using it for asthma patients with the syndrome of "lung qi deficiency, retention of fluid, and blood stasis" has the defects of "strong blood stasis-removing ability but weak lung-tonifying ability, insufficient fluid-resolving ability and neglecting the nasal passages", making it difficult to comprehensively cover the complex pathogenesis of "deficiency, fluid, stasis, and sensitivity" intertwined in this syndrome type, resulting in unstable clinical efficacy and limited long-term effects on reducing acute attacks and improving the quality of life. Other traditional Chinese medicine compound prescriptions or characteristic therapies, such as Xiaoqinglong Decoction, Yupingfeng Powder, etc., often tend to focus on treating the symptoms, or tend to treat the root cause, or are limited to a single syndrome type, lacking a systematic optimized formula that can simultaneously take into account multiple effects of "warming the lung to resolve fluid, promoting blood circulation to remove blood stasis, tonifying the lung to strengthen the root, and dredging the nasal passages to reduce sensitivity" for the complex syndrome type of "lung qi deficiency, retention of fluid, and blood stasis". In addition, existing traditional Chinese medicine compound prescriptions often have vague descriptions in the preparation process, dosage standards, and treatment course specifications, lacking a repeatable and quantifiable standardized plan, which affects their clinical promotion and efficacy stability.

[0006] To sum up, in the existing technology, Western medicine treatment has problems such as side effects, high costs, limited mechanisms, and neglect of overall regulation; while existing traditional Chinese medicine compound prescriptions, especially the original prescription of Guizhi Fuling Pills and its similar applications, have defects such as incomplete syndrome coverage, insufficient comprehensiveness of compatibility, and lack of standardized plans. The fundamental reason is that the profound understanding of the core pathogenesis of asthma during the non-acute attack period in traditional Chinese medicine has not been organically integrated with the research results of modern medicine on pathological mechanisms such as airway inflammation, neuroimmune regulation, and nose-lung association, thus failing to design a compound preparation with precise components, synergistic compatibility, treating both the symptoms and the root cause, and facilitating standardized production.

[0007] Therefore, there is an urgent need to provide a new traditional Chinese medicine composition that can precisely target the "lung deficiency, phlegm retention, and blood stasis syndrome" in the non-acute phase of asthma. Through scientific formulation, it can simultaneously achieve the comprehensive therapeutic goals of warming the lungs and resolving phlegm, promoting blood circulation and removing blood stasis, tonifying the lungs and strengthening the body, and clearing the orifices and reducing sensitivity, effectively improving symptoms, reducing acute attacks, and improving quality of life. Summary of the Invention

[0008] The purpose of this invention is to provide a traditional Chinese medicine composition and its preparation method for treating non-acute asthma attacks, thereby addressing the problems existing in the prior art. This invention combines traditional Chinese medicine syndrome differentiation with modern pathological mechanisms, providing a treatment plan that is precisely formulated, has a clear mechanism, definite efficacy, and high safety. It effectively solves the problems of incomplete syndrome coverage in existing traditional Chinese medicine compound prescriptions and the significant side effects and singular mechanisms of Western medicine treatments, providing a new option for the clinical treatment of non-acute asthma attacks (lung deficiency, phlegm retention, and blood stasis syndrome).

[0009] To achieve the above objectives, the present invention provides the following solution:

[0010] This invention provides a traditional Chinese medicine composition for treating non-acute exacerbations of asthma, comprising the following ingredients in equal weight proportions: cinnamon twig, poria cocos, peach kernel, red peony root, peony bark, ginger, jujube, prepared licorice root, magnolia flower, and cocklebur.

[0011] Optional, by weight, the ingredients include 10 parts cinnamon twig, 10 parts poria cocos, 10 parts peach kernel, 10 parts red peony root, 10 parts peony bark, 10 parts ginger, 10 parts jujube, 10 parts prepared licorice root, 10 parts magnolia flower, and 10 parts cocklebur.

[0012] The present invention also provides the application of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for treating non-acute exacerbations of asthma.

[0013] The present invention also provides a medicament for treating non-acute exacerbations of asthma, the active ingredient of which includes the aforementioned traditional Chinese medicine composition.

[0014] Optionally, the drug may also include pharmaceutically acceptable excipients.

[0015] Optionally, the dosage form of the drug includes decoctions and concentrated pills.

[0016] The present invention also provides a method for preparing the aforementioned drug. When the drug is a decoction, the method includes the following steps: taking the raw material in the specified weight proportions, adding 12 times the amount of water, soaking and then decocting for the first time, filtering, collecting the first decoction, adding 8 times the amount of water to the decocted residue, decocting for the second time, filtering, collecting the second decoction, combining the two decoctions and concentrating to obtain the decoction.

[0017] When the drug is a concentrated pill, the following steps are included: taking the raw material in the specified weight parts and pulverizing it, adding 10 times the amount of water to the powder for dynamic reflux extraction, sieving and concentrating the extract to obtain a clear extract, adding excipients to the clear extract, spray drying to obtain a dry extract powder, adding flavoring agents to the dry extract powder, mixing and sieving, and preparing the concentrated pill.

[0018] Optionally, when the medicine is a decoction, the soaking time is 40 minutes.

[0019] Optionally, when the medicine is a decoction, the first decoction time is 35 minutes and the second decoction time is 25 minutes.

[0020] Optionally, when the drug is a concentrated pill, the temperature of the dynamic reflux extraction is 80-85℃, the extraction is performed twice, and each extraction lasts for 2.5 hours.

[0021] The present invention discloses the following technical effects:

[0022] This invention addresses the shortcomings of existing technologies in treating "lung deficiency with fluid retention and blood stasis syndrome" during non-acute asthma attacks through a "four-dimensional synergistic effect" formulation. It uses cinnamon twig and poria as the principal ingredients to warm and transform fluid retention, strengthen the spleen and benefit the lungs, directly targeting the core pathogenesis of "fluid retention" and "lung deficiency," overcoming the shortcomings of the traditional Guizhi Fuling Wan formula, which "does not tonify the lungs and is weak in transforming fluid retention." Peach kernel, red peony root, peony bark, and ginger are used as assistant ingredients to strengthen the transformation of blood stasis, anti-inflammation, and dispelling cold and fluid retention, compensating for the deficiencies of Western medicine treatments that "only block a single inflammatory pathway and neglect neuro-immune interaction disorders." Jujube, magnolia flower, and cocklebur are added to tonify the lungs, strengthen the body's foundation, and clear the nasal passages and reduce sensitivity, supplementing the shortcomings of existing TCM compound formulas that "neglect the nasal-lung connection and are insufficient in strengthening the body's foundation." Prepared licorice root harmonizes the entire formula, ensuring that warming and transforming fluid retention does not cause dryness and that transforming blood stasis does not harm the body's vital energy. This formulation system achieves a three-dimensional intervention of "resolving blood stasis and treating the symptoms, tonifying the lungs and consolidating the foundation, and clearing the orifices and reducing sensitivity", which precisely covers the treatment needs of the complex pathogenesis of "deficiency, phlegm, blood stasis and sensitivity" in this syndrome from a mechanistic perspective.

[0023] Animal experiments have verified that the composition of this invention is significantly effective in improving the core pathological aspects of asthma. In a mouse model of asthma established by OVA sensitization combined with cold stimulation, the modified Guizhi Xinyi Wan of this invention can effectively reduce inflammatory cell infiltration in lung tissue, inhibit hypersecretion of airway epithelial mucus, reduce peri-airway collagen deposition, and improve airway remodeling. Its efficacy is comparable to that of the positive control drug dexamethasone and superior to the classic formula Guizhi Fuling Wan. This experimentally verifies the scientific validity of the synergistic effect of the multiple functions of "resolving blood stasis, eliminating phlegm, strengthening the body, and clearing the orifices" of this invention, confirming that it can provide multi-target intervention for the complex pathological state of "lung deficiency, phlegm retention, and blood stasis syndrome" in the non-acute exacerbation phase of asthma, providing reliable pharmacodynamic evidence for clinical application. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 HE staining microscopic images of lung tissue from each group of mice (A) and scoring statistics (B).

[0026] Figure 2 Microscopic observation of AB / PAS staining of lung tissue in each group of mice (A) and scoring statistics (B);

[0027] Figure 3 Masson staining microscopic images (A) and quantitative statistical graphs (B) of lung tissue from each group of mice. Detailed Implementation

[0028] This invention is based on the theory that "the core pathogenesis of asthma in the non-acute exacerbation period is lung deficiency, phlegm retention, and blood stasis." It uses the classic formula Guizhi Fuling Wan as the basic framework and innovatively adds ginger, jujube, and prepared licorice to strengthen the "foundation-strengthening" effect. It also combines magnolia flower and cocklebur to optimize the "opening of the orifices and desensitization" effect, forming a traditional Chinese medicine composition for treating asthma in the non-acute exacerbation period with the triple effects of "treating the symptoms, strengthening the foundation, and preventing induction."

[0029] The traditional Chinese medicine composition of the present invention is composed of 10 raw materials, namely cinnamon twig, poria cocos, peach kernel, red peony root, peony bark, ginger, jujube, prepared licorice root, magnolia flower and cocklebur, in equal proportions by weight. The core efficacy and target correlation of each component are shown in Table 1.

[0030] Table 1. Core efficacy and target association of each component

[0031]

[0032] In one specific embodiment of the present invention, the weight of each of the above 10 raw materials is 10g.

[0033] The herbal composition of this invention strictly follows the TCM principle of "principal, assistant, adjuvant, and guide" in drug formulation. Each component has a clear division of labor and works synergistically to form a four-dimensional efficacy system of "warming the lungs and resolving phlegm + promoting blood circulation and removing blood stasis + tonifying the lungs and strengthening the body + clearing the orifices and reducing sensitivity." This system precisely covers the key points of the pathogenesis of "lung deficiency, phlegm retention, and blood stasis." The specific logic is as follows:

[0034] The principal herbs (cinnamon twig and poria, the core and leading herbs): Cinnamon twig is pungent and warm, which can dispel wind and cold from the exterior to relieve the symptoms of the exterior of the body, warm the interior to transform water retention, and enter the blood to help resolve blood stasis; Poria promotes diuresis and eliminates dampness to remove "water retention", and strengthens the spleen and benefits the lungs to replenish "lung deficiency" - the combination of the two directly targets the core of "yang deficiency and water retention, and lung qi deficiency", laying the foundation for the efficacy of the whole formula and solving the defects of the original Guizhi Fuling Wan formula that "does not replenish the lungs and is weak in transforming water retention".

[0035] Assistant herbs (peach kernel, red peony root, peony bark, and ginger, working synergistically): Peach kernel, red peony root, and peony bark together form the core of "invigorating blood and removing blood stasis," synergistically improving airway microcirculation disorders and inhibiting local inflammation; ginger is pungent and warm, dispelling cold, which not only helps cinnamon twig to relieve exterior symptoms and resolve phlegm, but also warms and transforms dampness in the middle jiao, preventing the recurrence of "phlegm retention." These four herbs, on the one hand, strengthen the "warming and blood stasis-resolving" effect of the principal herbs, and on the other hand, balance the pungent and warm dryness of cinnamon twig, preventing dryness from damaging the lungs, thus solving the problem of "blood stasis without anti-inflammation and incomplete phlegm resolution" in the existing treatment.

[0036] The adjuvant herbs (jujube, magnolia flower, and cocklebur, for strengthening the body and reducing allergies): Jujube replenishes the middle and boosts qi, working synergistically with the principal herb Poria and the assistant herb ginger to "strengthen the spleen and lungs," protecting the acquired constitution to strengthen the body's foundation; magnolia flower and cocklebur are specifically for "opening the nasal passages and desensitizing," specifically improving nasal mucosal sensitization and cutting off the "nasal-lung reflex" triggering pathway. The three herbs supplement the dimensions of "strengthening the body's foundation" and "preventing induction," addressing the shortcomings of existing compound formulas that "neglect the nasal-lung connection and are insufficient in strengthening the body's foundation."

[0037] The use of prepared licorice root to invigorate qi and harmonize the middle jiao not only enhances the effect of "tonifying the lungs and strengthening the foundation," but also harmonizes the pungent and warm (cinnamon twig, ginger) and cold (red peony root, peony bark) properties of the whole formula, and mitigates the irritation of peach kernel and cocklebur, ensuring that the efficacy of each component is synergistic and unbiased, and improving the safety and stability of the formula.

[0038] The above-mentioned traditional Chinese medicine composition of the present invention can be prepared into decoctions and concentrated pills, etc.

[0039] Decoction: Suitable for patients with obvious symptoms of asthma during non-acute exacerbations (such as chest tightness, cough, and clear, thin sputum 1-2 times per week). One dose per day, divided into three warm doses in the morning, noon, and evening, 200mL each time. One course of treatment is 10 days. Two to three courses of treatment can be taken consecutively, with a three-day interval between courses to protect the spleen and stomach.

[0040] Concentrated pills: Suitable for patients with stable symptoms of asthma during non-acute exacerbations (≤1 exacerbation per month) who require long-term prevention. Take 5-6 pills (containing 3-3.6g of raw herbs) 3 times a day with warm water. One month is one course of treatment. It is recommended to take 4 courses of treatment per year (1 course per quarter). The interval between courses of treatment can be adjusted according to lung function indicators (FEV1 / FVC≥70%).

[0041] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0042] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0043] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0044] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0045] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0046] Example 1

[0047] The prescription for the Chinese herbal combination is as follows: 10g of cinnamon twig, 10g of poria cocos, 10g of peach kernel, 10g of red peony root, 10g of peony bark, 10g of ginger, 10g of jujube, 10g of prepared licorice root, 10g of magnolia flower, and 10g of cocklebur.

[0048] Method for preparing a decoction for treating non-acute asthma attacks using the above-mentioned traditional Chinese medicine composition:

[0049] (1) Take the above 10 raw materials, remove impurities and wash them separately; among them, magnolia flower and cocklebur are wrapped in clean gauze for later use; remove the pits from the jujubes and cut them into thin slices; wash the ginger and slice it for later use.

[0050] (2) Place all the pretreated medicinal materials into a decoction container, add 1200 mL of purified water, and soak for 40 minutes.

[0051] (3) First bring to a boil over high heat, then reduce to low heat and continue simmering for 35 minutes. Filter and collect the first decoction.

[0052] (4) Add 800 mL of purified water to the dregs after decoction, bring to a boil again over high heat, then simmer over low heat for 25 minutes, filter, and collect the second decoction.

[0053] (5) Combine the decoctions obtained from the two decoctions, heat and concentrate to 600 mL to obtain the finished decoction.

[0054] The prepared decoction should be consumed within 24 hours at room temperature, or stored in a sealed container at 4°C for no more than 7 days. It should be heated to a suitable temperature before consumption.

[0055] Dosage: Suitable for patients with obvious symptoms of asthma during non-acute exacerbations (such as chest tightness, cough, and clear, thin sputum 1-2 times per week). Take 200mL of warm medicine three times a day, morning, noon and evening. One course of treatment is 10 days. Take 2-3 courses of treatment consecutively, with a 3-day interval between courses to protect the spleen and stomach.

[0056] Example 2

[0057] The prescription for the Chinese herbal combination is as follows: 10g of cinnamon twig, 10g of poria cocos, 10g of peach kernel, 10g of red peony root, 10g of peony bark, 10g of ginger, 10g of jujube, 10g of prepared licorice root, 10g of magnolia flower, and 10g of cocklebur.

[0058] A method for preparing concentrated pills for treating non-acute asthma attacks using the above-mentioned traditional Chinese medicine composition:

[0059] (1) Take the above 10 raw materials, mix them evenly according to the proportion, and crush them into coarse powder (pass through a 10-mesh sieve).

[0060] (2) Place the crude powder in a dynamic extraction tank, add 10 times the amount of purified water (based on the total weight of the raw drug), heat to 80-85℃, and perform dynamic reflux extraction. Extract twice, 2.5 hours each time, and combine the two extracts.

[0061] (3) Filter the combined extract through a 120-mesh sieve to remove the residue and obtain a clear liquid.

[0062] (4) The filtered liquid is transferred into a vacuum concentration device and concentrated under vacuum conditions of -0.08 ~ -0.06 MPa and temperature of 60-65℃ until a clear paste with a relative density of 1.25-1.30 (measured at 60℃) is obtained.

[0063] (5) Add 12% of the weight of dextrin and 5% of the weight of soluble starch to the clear paste and stir to mix evenly.

[0064] (6) Spray dry the mixture, set the inlet air temperature to 180-190℃ and the outlet air temperature to 80-85℃, to obtain dry extract powder with a moisture content of ≤5%.

[0065] (7) Add 8wt% honey water (as a binder) to the dry extract powder and mix to obtain a soft material.

[0066] (8) Granulate the soft material through a 14-mesh sieve, dry the resulting wet granules at 50-55℃ until the moisture content is ≤3%, and then granulate.

[0067] (9) The granules are made into concentrated pellets with a diameter of 3-4 mm by using the pan pelleting method.

[0068] (10) Coat the concentrated pills with a thin film of hydroxypropyl methylcellulose solution and dry to obtain the finished pill product. Each pill contains 0.6g of raw drug.

[0069] Dosage: Suitable for patients with stable symptoms of asthma during non-acute exacerbations (≤1 exacerbation per month) who require long-term prevention. Take 5-6 pills (containing 3-3.6g of raw herbs) 3 times a day with warm water. One month is one course of treatment. Take 4 courses of treatment per year (1 course per quarter). The interval between courses of treatment can be adjusted according to lung function indicators (FEV1 / FVC≥70%).

[0070] Comparative Example

[0071] The only difference from Example 2 is that the prescription of the traditional Chinese medicine composition is: 10g of cinnamon twig, 10g of poria cocos, 10g of peach kernel, 10g of red peony root, and 10g of peony bark.

[0072] Effect verification example

[0073] 1. Experimental materials

[0074] Experimental animals: Female BALB / c mice, weighing 18-22 g, were housed at the Experimental Animal Center of Guangzhou University of Chinese Medicine, with free access to food and water, and were acclimatized for one week. This experiment was approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine (Ethics Number: 20241107004).

[0075] Test drug:

[0076] Enhanced Cinnamon Twig and Magnolia Flower Pill: Prepared according to the raw materials and methods of Example 2, and dissolved in pure water to the required concentration of the medicine before use;

[0077] Guizhi Fuling Pill (positive control): prepared according to the raw materials and methods of the comparative ratio.

[0078] Main reagents and instruments:

[0079] Ovalbumin (OVA, Grade III, Sigma, Catalog No. A5530), Freund's complete adjuvant (CFA, Sigma, Catalog No. F5881), physiological saline, mouse-specific nebulizer (Model HY-JSE01, nebulization rate 0.2 mL / min).

[0080] 2. Experimental Methods

[0081] 2.1 Animal grouping and administration

[0082] Fifty female BALB / c mice were randomly divided into 5 groups, with 3 mice in each group:

[0083] Normal control group (Con): No model was established, and the same volume of physiological saline was administered by gavage.

[0084] Asthma model group (Mod): OVA sensitization and challenge, followed by gavage administration of an equal volume of physiological saline.

[0085] Model + Low Temperature Group (Mod + Cold): OVA sensitization and stimulation were combined with cold stimulation, followed by gavage administration of an equal volume of physiological saline.

[0086] Guizhi Fuling Wan group (GFW): OVA sensitization and stimulation were combined with cold stimulation, and Guizhi Fuling Wan liquid was administered by gavage (at a raw drug dosage of 31.6 g / kg).

[0087] The modified Guizhi Xinyi Pill group (GXY): OVA sensitization and stimulation were combined with cold stimulation, and the modified Guizhi Xinyi Pill liquid of the present invention was administered by gavage (at a raw drug dosage of 31.6 g / kg).

[0088] The gavage volume was 0.2 mL / 10g body weight, once daily, starting from day 1 of the stimulation period and continuing until the end of the experiment.

[0089] 2.2 Establishment of a mouse model of asthma combined with cold stimulation

[0090] Sensitization phase: On days 0, 7, and 14 of the experiment, mice in each model group (Mod, Mod+Cold, GFW, and GXY) were sensitized. 20 μg of OVA and 75 μL of CFA were thoroughly emulsified, and physiological saline was added to make up to a total volume of 300 μL per mouse, which was then administered to each mouse via intraperitoneal injection.

[0091] Challenge phase: From day 21 to day 30 of the experiment, the mice in the above-mentioned model group were challenged daily. The mice were placed in a self-made nebulizer and inhaled 5% OVA solution at a nebulization rate of 0.2 mL / min for 40 minutes.

[0092] Cold stimulation: During the provocation phase, after each day's OVA nebulization, the Mod+Cold, GFW, and GXY mice were immediately transferred to a 4-10℃ cold room for 4 hours of exposure, twice daily (once in the morning and once in the afternoon). The normal control group and the simple model group (Mod) were kept in a room temperature environment.

[0093] Model evaluation: Observe and record behavioral changes in mice during the provocation period, such as typical asthma-like symptoms such as rubbing nose, sneezing, rapid breathing, head nodding, cyanosis of the lips, abdominal breathing, arched back, hair standing on end, and abdominal muscle twitching.

[0094] 2.3 Sample Collection and Processing

[0095] Twenty-four hours after the last challenge, mice were anesthetized by intraperitoneal injection of 3% sodium pentobarbital (45 mg / kg). Blood was collected from the abdominal aorta, serum was separated, and stored at -80°C. Mice were then sacrificed, endotracheally intubated, and bronchoalveolar lavage was performed with pre-chilled PBS. The lavage fluid (BALF) was recovered, centrifuged, and the supernatant was used for subsequent analysis. Lung tissue was completely harvested, rinsed with pre-chilled PBS, and blotted dry with filter paper. The left lung was fixed in 4% paraformaldehyde for pathological examination; the right lung was rapidly cryopreserved in liquid nitrogen and then transferred to -80°C for molecular biological analysis.

[0096] 2.4 Lung tissue pathological examination

[0097] Paraffin section preparation: The fixed left lung tissue was dehydrated by gradient ethanol, cleared with xylene, embedded in paraffin, and then continuously sectioned along the coronal plane with a thickness of 5 μm.

[0098] (1) HE staining of paraffin sections: ① Dewaxing paraffin sections to water: Dewax the paraffin sections and then wash them with tap water; ② PAS staining B and A: Place the sections in PAS staining B and A (protected from light) for 15 minutes and 30 minutes respectively, and then rinse with running water for 5 minutes; ③ PAS staining C: Place the sections in PAS staining C for 30 seconds, then differentiate them with hydrochloric acid solution, then wash with tap water, blue them with ammonia, and finally rinse with running water; ④ Dehydration and mounting: Gradually place the treated sections into anhydrous ethanol I, anhydrous ethanol II, anhydrous ethanol III, xylene I, and xylene II for clearing treatment, and then mount them with neutral resin; ⑤ Microscopic examination: After the mounted sections are dry, perform image analysis. The HE staining scoring criteria for mouse lung tissue are shown in Table 2.

[0099] Table 2 HE staining scoring criteria for mouse lung tissue

[0100]

[0101] (2) AB / PAS staining of paraffin sections: ① Dewaxing paraffin sections to water: Place the sections in environmentally friendly dewaxing and clearing solution I for 15 min, environmentally friendly dewaxing and clearing solution II for 15 min, anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, and 75% ethanol for 5 min, then rinse with tap water; ② Restoration and fixation of frozen sections: Remove the frozen sections from the -20℃ freezer and restore them to room temperature. Fix them with tissue fixative for 15 min, then rinse with running water; ③ Staining with AB-PAS staining solution C: Stain the sections in AB-PAS staining solution C for 15 min, then rinse with tap water until colorless; ④ Acidification with AB-PAS staining solution B: Stain the sections in AB-PAS staining solution B for 15 min, then rinse with tap water and distilled water twice; ⑤ Staining with AB-PAS staining solution A: Stain the sections in AB-PAS staining solution A (restoring room temperature) in the dark for 1 h, then rinse with running water for 5 min; ⑥ Dehydration and mounting: Place the sections in anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, and anhydrous ethanol III for 5 min. 5 min - Xylene I 5 min - Xylene II 5 min Clearing, neutral resin mounting; ⑦ Microscopic examination, image acquisition and analysis. Positively stained AB / PAS cells were identified using a threshold method via a deconvolution module, followed by calibration and measurement in micrometers. Data are expressed as the percentage of AB / PAS-positive epithelial area divided by the total epithelial area (%PAS+ / total area).

[0102] (3) Masson staining of paraffin sections: ① Dewaxing paraffin sections to water: Follow the same dewaxing steps and wash with tap water; ② Masson staining solution A: Immerse the sections in Masson staining solution A overnight, and then wash with tap water; ③ Masson staining solutions B and C: Place the sections in a mixture of equal parts of Masson staining solutions B and C for 1 minute, then differentiate with 1% hydrochloric acid alcohol and wash with tap water; ④ Masson staining solution D: Immerse the sections in Masson staining solution D for 6 minutes, and then rinse with tap water. ⑤ Masson staining solution E treatment: Immerse the slides in Masson staining solution E for 1 minute; ⑥ Masson staining solution F treatment: Do not wash with water, drain slightly and then directly immerse in Masson staining solution F for 2-30 seconds; ⑦ 1% glacial acetic acid and anhydrous ethanol treatment: Rinse and differentiate with 1% glacial acetic acid, then dehydrate with two batches of anhydrous ethanol; ⑧ Clearing and mounting: Place the slides in a third batch of anhydrous ethanol for 5 minutes, then place them in xylene for 5 minutes to complete the clearing process, and finally mount with neutral resin; ⑨ Microscopic examination: Observe using a scanner and perform image acquisition and analysis.

[0103] 2.5 Statistical Analysis

[0104] Experimental data are expressed as mean ± standard deviation (x ± s). Statistical analysis was performed using GraphPad Prism 9.0 software (https: / / www.graphpad.com / ). For comparisons among multiple groups, if the data conformed to a normal distribution and had homogeneous variances, one-way ANOVA was used, and Dunnett's multiple comparison test was used for pairwise comparisons between groups; if the variances were unequal, Welch's ANOVA was used, and Dunnett's T3 test was used for comparisons between groups; if the data did not conform to a normal distribution, the nonparametric Kruskal-Wallis H test was used. A p-value < 0.05 was considered statistically significant.

[0105] 3. Experimental Results

[0106] 3.1 Model Building and Behavioral Observation

[0107] The day after sensitization, mice in the model group exhibited reduced activity, curling up, and loss of appetite. During the challenge period, mice in the model group (model group and model plus hypothermia group) gradually developed typical asthma symptoms such as restlessness, frequent nose rubbing, sneezing, irregular breathing rhythm, forelimb retraction and elevation, head nodding, cyanosis of the lips with obvious abdominal breathing, arched back, hair standing on end, and abdominal muscle twitching, which worsened with the increase of the challenge days. Cold stimulation further aggravated the above symptoms in the model group mice. The asthma-like behavioral manifestations of mice in the drug intervention groups (Guizhi Fuling Wan and Jiawei Guizhi Xinyi Wan) were reduced to varying degrees compared with those in the model group.

[0108] 3.2 Effects on inflammatory cell infiltration in lung tissue (HE staining)

[0109] In HE staining, the control group mice showed regular airway structure without narrowing, less inflammatory cell infiltration, neatly arranged bronchial epithelial cells without hyperplasia or hypertrophy, clear and intact alveolar morphology, no thickening of alveolar septa, no edema in the pulmonary interstitium, and no inflammatory cell exudation in the peribronchial vessels. In the model group / model group with added cold stimulation, the lung airway structure was irregular, the airway walls were thickened, and more mucus secretion was observed. Compared with the normal group, the airways were significantly narrowed, and a large number of inflammatory cells, mainly lymphocytes, macrophages, and neutrophils, were observed in the bronchi at all levels. Bronchial epithelial cells were swollen and detached, the alveolar walls were thinned and fractured, the alveolar septa were thickened, and there was increased peribronchial inflammatory cell outflow. The inflammation score was significantly higher than that of the normal group. Figure 1 P<0.05); Guizhi Fuling Wan and Jiawei Guizhi Xinyi Wan showed improvement compared to the model group, and the overall pathological changes were significantly different from those in the model group. Figure 1 (P < 0.05).

[0110] 3.3 Effects on hypersecretion of mucus in lung tissue (AB-PAS staining)

[0111] No PAS-positive staining (mucus) was observed in the airway epithelium of mice in the normal control group. In the model group and mice subjected to combined cold stimulation, numerous purplish-red PAS-positive areas were observed in the airway epithelium, with goblet cell proliferation and hypertrophy, and significantly increased mucus secretion. After drug intervention, the area and depth of AB / PAS-positive staining in the airway epithelium of mice in the Guizhi Fuling Wan group and the Jiawei Guizhi Xinyi Wan group were significantly reduced compared to the model group, and the mucus score decreased significantly (P < 0.05). The Jiawei Guizhi Xinyi Wan group showed a superior trend in reducing mucus secretion compared to the Guizhi Fuling Wan group. Figure 2 ).

[0112] 3.4 Effects on airway remodeling in lung tissue (Masson staining)

[0113] In the normal control group, only a small amount of blue collagen fibers were observed around the airways and in the alveolar septa of mice. In the model group and mice subjected to cold stimulation, the airway basement membrane thickened, the airway smooth muscle layer proliferated, and a large amount of blue collagen fibers were deposited around the airways and in the alveolar septa, suggesting increased collagen synthesis and airway remodeling. After drug intervention, the area of ​​blue collagen deposition around the airways in mice in the Guizhi Fuling Wan group and the Jiawei Guizhi Xinyi Wan group was significantly reduced compared to the model group (P < 0.05). Quantitative image analysis showed that the Jiawei Guizhi Xinyi Wan group was superior to the Guizhi Fuling Wan group in inhibiting collagen deposition and reducing airway remodeling. Figure 3 ).

[0114] The above efficacy verification examples established an asthmatic mouse model sensitized by OVA combined with cold stimulation. The efficacy of the traditional Chinese medicine composition of this invention was evaluated using a comprehensive range of pathological methods, including HE, AB / PAS, and Masson staining. The results showed that the traditional Chinese medicine composition provided by this invention can effectively reduce inflammatory cell infiltration in the lung tissue of asthmatic mice, inhibit airway epithelial mucus hypersecretion, reduce collagen deposition, and improve airway remodeling. Its efficacy is superior to the classic formula Guizhi Fuling Wan. This invention provides experimental evidence for the application of the traditional Chinese medicine composition in treating non-acute asthma attacks (diagnosed in traditional Chinese medicine as lung deficiency with fluid retention and blood stasis).

[0115] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for treating non-acute exacerbations of asthma, characterized in that, The ingredients include cinnamon twigs, poria cocos, peach kernels, red peony root, peony bark, ginger, jujubes, prepared licorice root, magnolia flower, and cocklebur fruit in equal proportions by weight.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, By weight, the ingredients include 10 parts cinnamon twig, 10 parts poria cocos, 10 parts peach kernel, 10 parts red peony root, 10 parts peony bark, 10 parts ginger, 10 parts jujube, 10 parts prepared licorice root, 10 parts magnolia flower, and 10 parts cocklebur.

3. The use of a traditional Chinese medicine composition as described in claim 1 or 2 in the preparation of a medicament for treating non-acute exacerbations of asthma.

4. A drug for treating non-acute exacerbations of asthma, characterized in that, The active ingredients include the traditional Chinese medicine composition as described in claim 1 or 2.

5. The drug according to claim 4, characterized in that, The drug also includes pharmaceutically acceptable excipients.

6. The drug according to claim 4, characterized in that, The dosage forms of the drug include decoctions and concentrated pills.

7. A method for preparing a drug as described in any one of claims 4-6, characterized in that, When the medicine is a decoction, the following steps are included: take the raw medicine in the specified weight, add 12 times the amount of water, soak and then decoct for the first time, filter, collect the first decoction, add 8 times the amount of water to the decocted residue, decoct for the second time, filter, collect the second decoction, combine the two decoctions and concentrate to obtain the decoction. When the drug is a concentrated pill, the following steps are included: taking the raw material in the specified weight parts and pulverizing it, adding 10 times the amount of water to the powder for dynamic reflux extraction, sieving and concentrating the extract to obtain a clear extract, adding excipients to the clear extract, spray drying to obtain a dry extract powder, adding flavoring agents to the dry extract powder, mixing and sieving, and preparing the concentrated pill.

8. The preparation method according to claim 7, characterized in that, When the medicine is a decoction, the soaking time is 40 minutes.

9. The preparation method according to claim 7, characterized in that, When the medicine is a decoction, the first decoction time is 35 minutes and the second decoction time is 25 minutes.

10. The preparation method according to claim 7, characterized in that, When the drug is a concentrated pill, the temperature of the dynamic reflux extraction is 80-85℃, the extraction is performed twice, and each extraction lasts for 2.5 hours.

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