Traditional Chinese medicine prescription for treating chronic duration of cough variant asthma in children and preparation method of traditional Chinese medicine prescription

Abstract

The invention discloses a traditional Chinese medicine prescription for treating chronic duration of children cough variant asthma and a preparation method of the traditional Chinese medicine prescription. The traditional Chinese medicine prescription is prepared from the following raw material medicines in parts by weight: 10 parts of radix pseudostellariae, 10 parts of angelica sinensis, 10 parts of raw rhizoma atractylodis macrocephalae, 10 parts of poria cocos, 10 parts of prepared rehmannia root, 6 parts of processed rhizoma pinelliae, 6 parts of pericarpium citri reticulatae and 3 parts of fresh ginger. Through intervention of the traditional Chinese medicine prescription, asthma can be effectively controlled, the disease course is shortened, the disease attack degree is improved, application of glucocorticoid is reduced, and finally the clinical curative effect of asthma is improved.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to a traditional Chinese medicine formula for treating the chronic persistent phase of cough variant asthma in children and its preparation method. Background Technology

[0002] Asthma, especially cough-variant asthma, is a common chronic airway disease in childhood, and its effective control has always been a serious challenge in clinical practice. Cough-variant asthma, a special type of bronchial asthma, is characterized by chronic airway inflammation and airway hyperresponsiveness, primarily manifesting as cough without significant wheezing attacks. This characteristic makes the disease easily overlooked clinically. However, its chronic airway inflammation persists for a long time, significantly impacting prognosis.

[0003] In recent years, the prevalence of asthma has shown a continuous upward trend globally, especially among young children. Despite the existence of various treatment methods, the control rate of asthma remains unsatisfactory. In Europe, more than half of asthma patients fail to achieve asthma control standards even with medication, with the proportions being 55.0%, 56.6%, and 53.5% in 2006, 2008, and 2010, respectively (Demoly P, Annunzita K, Gubba E, et al. Repeated cross-sectional survey of patients. reported asthma control in Europe in the past 5 years[J]. Eur Respir Rev, 2012, 21(123):66-74). Studies show that only 3.0% of Asian children with asthma achieve complete control, 44.0% achieve partial control, and a staggering 53.0% achieve no control (Wong GW, Kwon N, Hong JG, et al. Pediatric asthma control in Asia: phase 2 of the Asthma Insights and Reality in Asia-Pacific (AIRIAP 2) survey[J]. Allergy, 2013, 68(4): 524-530.). This is far below the ideal level, highlighting the arduous task of asthma control.

[0004] Traditional Chinese medicine (TCM) believes that the name "chronic cough variant asthma" should correspond to "asthma." The basic pathogenesis of persistent asthma is the presence of phlegm latent in the lungs. The pathological factor is primarily phlegm, which is mainly produced due to the lungs' inability to distribute fluids, spleen dysfunction, and kidney's inability to govern water, leading to the accumulation of body fluids into phlegm, which then lies dormant in the lungs, becoming the "root cause" of the persistent condition. Children have the physiological characteristics of "frequent lung deficiency," "frequent spleen deficiency," and "frequent kidney deficiency." Wan Quan, a famous physician of the Ming Dynasty, believed that children's "lungs are delicate organs," "as weak as a honeycomb," and "damaged lungs are difficult to heal." Therefore, lung qi deficiency is the primary condition for the onset of childhood asthma. The *Xiao'er Yaozheng Zhijue* states: "Lung disease presents with stuffiness, choking, frequent exhalations, shortness of breath, and wheezing." The *Suwen* (Plain Questions) states: "The spleen is the foundation of acquired constitution, governing the transformation and transportation of the essence of water and grain, and is the source of qi and blood." Children's constitution, characterized by deficiencies in the lungs, spleen, and kidneys, determines the difference between the chronic persistent phase of childhood asthma and that of adults. This is primarily manifested in a greater tendency to accumulate phlegm and dampness internally, obstructing the lung channels, and causing the condition to remain in a persistent phase. At this stage, symptoms such as wheezing and coughing are largely relieved compared to the acute phase, but this does not indicate a complete cure. Rather, it signifies that phlegm remains dormant within the body. Asthma is a protracted disease, significantly damaging the yang energy of the internal organs. The lungs, being the primary site of the disease, are easily invaded by cold and dampness. Once triggered by external pathogens, the latent phlegm is aroused, leading to an asthma attack.

[0005] The incidence of chronic cough-variant asthma in children is rising year by year, and the overall control level of childhood asthma is not ideal. This is mainly attributed to several factors, including the fear of children and their families regarding long-term use of inhaled corticosteroids, neglect of treatment in the middle and late stages of the disease, and a lack of professional and scientific knowledge about asthma. Poor adherence to asthma treatment is one of the important reasons for the poor overall control effect. The main reasons for poor compliance are as follows: First, adverse drug reactions are an important factor affecting the treatment compliance of children. Asthmatic children are currently treated mainly by long-term use of inhaled corticosteroids, which can effectively relieve local airway spasm and hyperresponsiveness and inhibit disease progression (Shen Kunling, Li Yunzhu, Li Changchong et al. Expert consensus on the application of nebulized inhalation therapy of corticosteroids in pediatrics [J], Journal of Clinical Pediatrics. 2011, 29(1):86-91.). However, long-term use of the drug can cause adverse reactions such as hoarseness, oral candidiasis, and respiratory discomfort. In severe cases, it can even cause symptoms such as peptic ulcers or obesity, which seriously affect the health and growth of children. This leads to resistance and paralysis of children and parents, resulting in non-compliance with medical advice, which seriously affects the subsequent treatment effect. Secondly, neglecting follow-up treatment and the belief that medication is unnecessary after acute exacerbation symptoms subside, with children and their families waiting until symptoms return before resuming medication, is problematic. Even though symptoms have subsided, airway hyperresponsiveness persists, increasing the risk of relapse. Relapse not only increases the financial burden on the family but also causes significant suffering for the child. Furthermore, the optimal period for consolidating treatment efficacy is missed. Thirdly, children and their families often lack professional and scientific knowledge about asthma, are unfamiliar with treatment plans, and have a weak awareness of health, severely impacting treatment adherence. The adverse reactions from long-term medication, neglect of follow-up treatment, and lack of asthma knowledge all seriously affect treatment adherence, consequently impacting asthma control.

[0006] Western medicine's treatment of persistent asthma primarily focuses on addressing local airway inflammation, lacking a holistic approach to systemic immune dysfunction and the long-term presence of atopic constitution. Consequently, long-term efficacy is often unsatisfactory. In contrast, Traditional Chinese Medicine (TCM) emphasizes a holistic approach in treating persistent asthma, guided by the principle of "strengthening the body's resistance and consolidating its foundation." By regulating and improving the patient's atopic constitution and immune dysfunction, it aims to prevent asthma attacks and achieve long-term remission.

[0007] Therefore, developing a new method or drug that can effectively control asthma and improve treatment adherence in children is of great significance for improving the quality of life of children with asthma and reducing the burden on families and society. Summary of the Invention

[0008] This invention relates to a drug for treating chronic persistent cough variant asthma in children and its preparation method, aiming to address the deficiencies in existing treatments for persistent asthma, particularly the shortcomings of Western medicine in terms of overall intervention and long-term efficacy.

[0009] To achieve the above object of the present invention, the following technical solutions are specifically adopted:

[0010] In the first aspect of the present invention, a traditional Chinese medicine formula for treating chronic persistent stage of childhood cough variant asthma is provided. The traditional Chinese medicine formula is prepared from raw medicinal materials including the following parts by weight: 10 parts of Pseudostellaria heterophylla, 10 parts of Angelica sinensis, 10 parts of Rhizoma Atractylodis Macrocephalae, 10 parts of Poria cocos, 10 parts of Rehmannia glutinosa, 6 parts of Rhizoma Pinelliae Praeparatum, 6 parts of Pericarpium Citri Reticulatae, and 3 parts of Zingiber officinale.

[0011] In the traditional Chinese medicine formula of the present invention, Rhizoma Pinelliae Praeparatum, Pericarpium Citri Reticulatae, Poria cocos, Rhizoma Atractylodis Macrocephalae combined with Angelica sinensis and Rehmannia glutinosa mainly focus on regulating and tonifying the lung and kidney, resolving phlegm and lowering adverse qi. According to the physical characteristics of children with insufficient lung, spleen, and kidney, the remission stage of childhood cough variant asthma is different from that of adults, mainly manifested in being more likely to produce internal accumulation of phlegm-dampness, obstruction of lung collaterals, and the condition is likely to stay in the remission stage and not heal for a long time. At this stage, symptoms such as wheezing and coughing have generally subsided, but it does not mean that the condition has been cured, but rather a state of latent phlegm remaining inside. Pseudostellaria heterophylla has a sweet taste and a neutral nature. Adding Pseudostellaria heterophylla to the traditional Chinese medicine formula is suitable for the physiological characteristics of children with insufficient lung and spleen at this stage. Pinellia ternata is pungent and warm, can dry dampness and resolve phlegm, and harmonize the stomach and stop vomiting; Pericarpium Citri Reticulatae is aromatic, can regulate qi and promote the function of the spleen, dry dampness and resolve phlegm; Pseudostellaria heterophylla is sweet and neutral, can benefit qi and strengthen the spleen, promote the production of body fluid and moisten the lung; Poria cocos is sweet and light, sweet can tonify the spleen, light can promote diuresis, so that the accumulated dampness is excreted through urine, and together with Glycyrrhiza uralensis to harmonize the middle and benefit the spleen, they jointly achieve the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm. Adding Angelica sinensis and Rehmannia glutinosa to nourish yin and replenish blood, to help restore the functions of the lung and kidney in governing qi and receiving qi, and together with the Erchen Decoction to regulate qi and strengthen the spleen, dry dampness and resolve phlegm. Zingiber officinale is pungent and warm, can enhance the effect of warming the lung and resolving phlegm. In this way, the spleen qi is healthy and transported, damp-phlegm is not generated, the lung has no turbid phlegm, then it is clear, peaceful, and descending, the yin of the lung and kidney is restored, qi can return to its root, and various symptoms such as coughing, wheezing, vomiting, and nausea can gradually recover. "When not yet occurring, focus on strengthening healthy qi, when already occurring, focus on attacking pathogenic qi urgently." During the remission period, strengthen healthy qi, strengthen the spleen to generate the lung, regulate the functions of its zang-fu organs, and remove the cause of phlegm production, so as to reduce and stop attacks and gradually achieve the purpose of radical cure.

[0012] The traditional Chinese medicine formula of the present invention can be made into various common dosage forms according to the techniques well-known to those skilled in the art, such as tablets, granules, capsules, pills, powders, oral liquid preparations.

[0013] In a specific embodiment, the traditional Chinese medicine formula of the present invention further contains pharmaceutically acceptable excipients, and the pharmaceutically acceptable excipients are well-known to those skilled in the art.

[0014] In the second aspect of the present invention, a preparation method of the above traditional Chinese medicine formula is provided, and the preparation method is different according to different dosage forms.

[0015] When the traditional Chinese medicine formula is an oral liquid preparation, the following preparation method can be selected, including the following steps: weigh each raw material according to the weight parts, mix them, add water to decoct, collect the decoction, filter, and the obtained filtrate is the oral liquid preparation.

[0016] When the traditional Chinese medicine formula is in granule form, the following preparation method can be selected, including the following steps: weigh each raw material according to the weight parts, mix them, add water to decoct and concentrate to obtain a clear extract, spray dry to obtain a dry extract fine powder, add excipients to dry compress granules, dry, and granulate to obtain granules.

[0017] Alternatively: Weigh each raw material according to the weight proportions, mix them, add ethanol solution for reflux extraction, concentrate the extract to obtain a clear extract, spray dry to obtain a dry extract powder, add excipients, dry compress into granules, dry, and granulate to obtain granules.

[0018] Furthermore, during the granulation process, the auxiliary materials include binders, which are selected from cellulose or gum.

[0019] When the traditional Chinese medicine formula is a powder, the following preparation method can be selected, including the following steps: weigh each raw material after aging according to the weight parts, mix them, and the powder is obtained.

[0020] Compared with the prior art, the beneficial effects of the present invention include at least the following:

[0021] 1. Western medicine's treatment of persistent asthma mainly focuses on intervening in local airway inflammation, lacking a holistic approach to addressing systemic immune dysfunction and the long-term presence of atopic constitution. Therefore, long-term efficacy is often unsatisfactory. In contrast, Traditional Chinese Medicine (TCM) treatment of persistent asthma emphasizes a holistic approach, guided by the principle of "strengthening the body's resistance and consolidating its foundation," focusing on improving the patient's own disease-fighting abilities. Through the TCM formula of this invention, the patient's atopic constitution and immune dysfunction are regulated and improved, achieving the goal of preventing asthma attacks and achieving long-term remission. This TCM formula intervention can effectively control asthma, shorten the course of the disease, improve the severity of attacks, reduce the use of glucocorticoids, and ultimately improve the clinical efficacy of asthma treatment.

[0022] 2. The traditional Chinese medicine formula of this invention can inhibit the expression of inflammatory cytokines in the serum of children with persistent cough variant asthma, regulate the immune function of the children, improve the lung function of the children, and help improve the prognosis of the children, which has positive clinical value. Detailed Implementation

[0023] The embodiments of the technical solution of the present invention will be described in detail below with reference to the examples. The following embodiments are only used to illustrate the technical solution of the present invention more clearly, and are therefore only examples, and should not be used to limit the scope of protection of the present invention.

[0024] It should be noted that, unless otherwise stated, the technical or scientific terms used in this application should have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0025] Unless otherwise specified, all active pharmaceutical ingredients used in the following embodiments are commercially available.

[0026] Example 1

[0027] Weigh out the following raw materials after processing: 10g of Codonopsis pilosula, 10g of Angelica sinensis, 10g of Atractylodes macrocephala, 10g of Poria cocos, 10g of Rehmannia glutinosa, 6g of Pinellia ternata, 6g of Citrus reticulata peel, and 3g of Zingiber officinale. Mix them to obtain a powder. To demonstrate the therapeutic effect of this herbal formula on the chronic persistent phase of cough variant asthma in children, the following clinical trial was conducted:

[0028] 1. Randomization method

[0029] A parallel-controlled trial was conducted, with participants divided into a traditional Chinese medicine group (treatment group) and a Western medicine group (control group) in a 1:1 ratio. Randomization was employed, and a randomization table was created. To minimize subjective bias and ensure that patients in both groups were similar in age, sex, weight, and health status, the two groups were made as similar as possible. Children suspected of having persistent cough-variant asthma were assigned random numbers strictly according to their enrollment time and received treatment according to the group corresponding to their random number.

[0030] 2. Treatment course

[0031] Based on the characteristics of chronic persistent asthma, the course of treatment with the experimental drug was 3 months.

[0032] Follow-up period: After the course of treatment is completed, follow-up will be conducted once a month, and the follow-up period for each case will not be less than 3 months.

[0033] The Western medicine group was treated according to the "Guidelines for the Diagnosis and Prevention of Childhood Bronchial Asthma" (2016 edition) revised by the Editorial Board of the Chinese Journal of Pediatrics, Chinese Medical Association: budesonide / formoterol powder inhaler (80 / 4.5ug), twice daily, one inhalation each time. Budesonide / formoterol powder inhaler is manufactured by AstraZeneca, Sweden.

[0034] The traditional Chinese medicine treatment group used the powder prepared above, 65g / dose, twice a day, 32.5g each time, dissolved in 100-150ml of boiling water and taken after meals.

[0035] 3. Medicinal uses and efficacy of this formula in treating chronic persistent cough variant asthma.

[0036] The relevant data obtained from the clinical trials are as follows:

[0037] 1. After treatment, the TCM syndrome scores (including total scores for primary symptoms, secondary symptoms, and total score) in both groups decreased compared to before treatment, with a more significant decrease in the TCM group than in the Western medicine group. Regarding individual symptom scores, the TCM group showed significantly lower scores in cough, sputum production, nasal congestion and runny nose, and sneezing compared to the Western medicine group (all P < 0.05). Pulmonary function indicators for small airways, including MMEF75 / 25, MEF25, MEF50, and MEF75, all increased compared to before treatment, with a greater increase in the TCM group than in the Western medicine group (all P < 0.05). Eosinophil levels in both groups decreased significantly after treatment compared to before treatment (P < 0.05), and the TCM group showed significantly lower levels than the Western medicine group after treatment (P < 0.05). The TCM group demonstrated advantages over the Western medicine group in improving symptoms, signs, and pulmonary function.

[0038] 2. After treatment in both groups, in the traditional Chinese medicine group, 3 cases were clinically cured, 46 cases showed significant improvement, 0 cases improved, and 1 case was ineffective. In the Western medicine group, 1 case was clinically cured, 37 cases showed significant improvement, 11 cases improved, and 3 cases were ineffective. Statistical analysis showed a difference in the distribution of clinical efficacy between the treatment and control groups, with the treatment group showing a better distribution of effective clinical efficacy than the control group. The total effective rate in the treatment group was 98%, while the total effective rate in the control group was 94%. The chi-square test showed a statistically significant difference in total effective rates between the two groups (P < 0.05), indicating that the treatment group had superior clinical efficacy compared to the control group.

[0039] Conclusion: 1. The traditional Chinese medicine group is superior to the Western medicine group in improving symptoms and signs, shortening the course of clinical remission, reducing airway inflammation, and improving lung ventilation in children with cough variant asthma during the clinical remission period. The clinical efficacy is also superior to that of the Western medicine group. The traditional Chinese medicine formula of this invention is an effective formula for treating childhood asthma during the clinical remission period.

[0040] 2. No drug-related adverse reactions were observed in the clinical trials of the traditional Chinese medicine formulas, indicating high safety, few side effects, and high clinical value.

Claims

1. A traditional Chinese medicine formula for treating the chronic persistent phase of cough variant asthma in children, characterized in that, The traditional Chinese medicine formula is made from the following raw materials in parts by weight: 10 parts of Codonopsis pilosula, 10 parts of Angelica sinensis, 10 parts of Atractylodes macrocephala, 10 parts of Poria cocos, 10 parts of Rehmannia glutinosa, 6 parts of Pinellia ternata, 6 parts of Citrus reticulata peel, and 3 parts of fresh ginger.

2. The traditional Chinese medicine formula according to claim 1, characterized in that, The dosage form of the traditional Chinese medicine formula is tablets, granules, capsules, pills, powders, or oral liquid preparations.

3. The traditional Chinese medicine formula according to claim 1, characterized in that, The traditional Chinese medicine formula also contains medicinal excipients.

4. The method for preparing the traditional Chinese medicine formula according to claim 1, characterized in that, The traditional Chinese medicine formula is an oral liquid preparation. The preparation method includes the following steps: weigh each raw material according to the weight parts, mix them, add water to decoct, collect the decoction, filter, and the obtained filtrate is the oral liquid preparation.

5. The method for preparing the traditional Chinese medicine formula according to claim 1, characterized in that, The traditional Chinese medicine formula is in the form of granules. The preparation method includes the following steps: weigh each raw material according to the weight parts, mix them, add water to decoct and concentrate to obtain a clear extract, spray dry to obtain a dry extract fine powder, add excipients to dry compress granules, dry, and granulate to obtain granules. Alternatively: Weigh each raw material according to the weight proportions, mix them, add ethanol solution for reflux extraction, concentrate the extract to obtain a clear extract, spray dry to obtain a dry extract powder, add excipients, dry compress into granules, dry, and granulate to obtain granules.

6. The preparation method according to claim 5, characterized in that, During the granulation process, the auxiliary materials include binders, which are selected from cellulose or gum.

7. The method for preparing the traditional Chinese medicine formula according to claim 1, characterized in that, The traditional Chinese medicine formula is a powder, and the preparation method includes the following steps: weigh each raw material after aging according to the weight parts, mix them, and the powder is obtained.