CN111870681A

CN111870681A - Traditional Chinese medicine composition for treating asthma and application thereof

Info

Publication number: CN111870681A
Application number: CN202010841820.9A
Authority: CN
Inventors: 鹿振辉; 张惠勇; 张彤; 马子风; 薛玲娜; 李翠
Original assignee: Longhua Hospital Affiliated to Shanghai University of TCM
Current assignee: Longhua Hospital Affiliated to Shanghai University of TCM
Priority date: 2020-08-20
Filing date: 2020-08-20
Publication date: 2020-11-03
Anticipated expiration: 2040-08-20
Also published as: CN111870681B; WO2022037561A1

Abstract

The invention relates to a traditional Chinese medicine composition for treating asthma and application thereof, wherein the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 4.5 parts of tortoise-plastron glue, 4.5 parts of turtle shell glue, 3 parts of deerhorn glue, 6 parts of monkshood, 15 parts of negundo chastetree fruit, 9 parts of prepared rehmannia root, 6 parts of cocklebur fruit, 15 parts of raw astragalus root, 7.5 parts of fried codonopsis pilosula, 9 parts of epimedium herb, 6 parts of curculigo orchioides, 4.5 parts of spina gleditsiae, 15 parts of dried rehmannia root, 15 parts of mother-of-pearl, 15 parts of dandelion, 15 parts of oldenlandia diffusa, 7.5 parts of gypsum, 6 parts of baked ginger carbon and 4.5 parts of honey-fried. The formula of the invention not only has the functions of warming yang, ventilating lung, dispelling cold, tonifying primordial yin and primordial yang, and consolidating the lung and kidney deficiency of asthma, but also can regulate the immunologic function of human body, warm yang, replenish essence, and assist vital qi to eliminate pathogenic factors. Its advantages are: the curative effect is exact, the medication is safe, and the experimental result shows that no obvious abnormality is found by monitoring three general methods, liver and kidney functions and electrocardiogram.

Description

Traditional Chinese medicine composition for treating asthma and application thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating asthma and application thereof.

Background

Bronchial asthma (asthma for short) is a heterogeneous clinical syndrome, manifested by recurrent wheezing, shortness of breath, chest tightness and cough, characterized by airway inflammation, airflow obstruction and Airway Hyperresponsiveness (AHR), and is one of the most common diseases of chronic respiratory tract, affecting more than 3 hundred million people worldwide, and the number of asthma patients is on the increasing trend year by year. Asthma conditions are chronic and differentiated and cannot be cured, and the bottleneck and difficulty of the current standardized treatment regimen (GINA) remain major. Global asthma control initiatives in recent years the goal of asthma treatment has been to achieve "overall control of asthma", both to achieve current control and to reduce future risks, and long-term stepwise treatment regimens have been recommended for asthmatics, where inhaled glucocorticoids and long-acting beta-adrenoceptor agonists in western medicine are the treatment of choice for most asthmatics. Although most patients can benefit from the treatment, the side effects such as adrenal suppression, anaphylaxis and osteoporosis which are possibly generated by using the medicines for a long time can cause great reduction of treatment compliance of some patients, the disease condition can not be effectively controlled, even the disease condition is aggravated, and the quality of life of many patients is not improved, so that a new treatment scheme and measure needs to be searched. There are multiple phenotypic characteristics in asthma in clinic due to the difference of airway immune inflammatory reaction leading directions, and the treatment scheme has larger group/individual difference and needs multi-target intervention.

The theoretical basis of the prior art on the traditional medicine is as follows:

asthma belongs to the categories of asthma syndrome, phlegm and fluid retention, qi ascending and the like in the traditional Chinese medicine, and the traditional Chinese medicine has a long treatment history on asthma and accumulates abundant clinical practice experience. The "yang-warming method" is one of the main fundamental treatment principles for bronchial asthma, and the "phlegm-fluid drinker is advocated in the treatise on the exogenous febrile disease and miscellaneous diseases" by Zhang Zhongjing in the early Han dynasty, and should be combined with warm herbs.

The understanding of the pathological mechanism of the patients with symptoms (chronic duration and attack period) in traditional Chinese medicine and pharmacy mostly focuses on: deficiency (yang deficiency, qi deficiency), cold (deficiency cold, cold evil), wind (exowind, endogenous wind), phlegm, stasis and other five main pathological links, and there are also diseases between each link. The syndrome differentiation and type division of traditional Chinese medicine are divided into four main types of cold asthma, heat asthma, wind asthma, deficiency asthma and the like, wherein the heat asthma and the cold asthma belong to the syndrome characteristics of acute attack, and the wind asthma and the deficiency asthma are more suitable for the disease characteristics of chronic duration. The traditional Chinese medicine has the advantages of treating the bronchial asthma with chronic duration (refractory treatment): the traditional Chinese medicine compound intervention is firstly started from the whole of a sick person, and the medicine is taken from the perspective of the whole disease, so that the traditional Chinese medicine compound intervention has the advantages and characteristics of multiple targets, wide effect, difficult medicine resistance and the like, and meanwhile, the medicine formula is flexible, so that the means is more abundant; many researches show that the dosage of hormone (inhalation/oral administration) can be gradually reduced by long-term application of traditional Chinese medicine treatment, part of patients can completely remove the hormone, and the condition is easy to stabilize; the traditional Chinese medicine has a relatively wide immune regulation effect (commonly called as traditional Chinese medicine which can tonify deficiency and the like), can regulate and control the unbalanced state of the immune system of an asthma patient by methods of strengthening body resistance, eliminating evil and the like, improves the cellular immunity and airway defense function of the patient, and leads the patient to induce the repeated attack of asthma or obviously reduce the chronic duration due to upper airway infection; many of the traditional Chinese medicines have direct spasmolysis and asthma relieving, phlegm reducing and anti-inflammatory effects, can directly improve clinical symptoms and airway inflammation states of patients, enable asthma to achieve the control target more easily, and improve control stability.

Review of ancient books documents:

although the traditional Chinese medicine was early in the "internal classic" in the age of asthma, its symptoms are recorded, and the "plain questions" are: when the pathogenic wind is deficient, yang is attacked, it enters six fu-organs. When yin is received, it enters five zang organs. Entering six fu organs, it causes fever, sometimes lying down, and dyspnea and respiratory tract. "Cold weather in the pulse … … should be treated with . "dyspnea and drinking due to summer heat, sweating and restlessness. "" Fu can not lie down, but lie down and dyspnea, it is also a water-vapor passenger. "the disease is marked by symptoms of edema of the elbow, large abdomen, dyspnea and insomnia. So the lung is dyspnea and the kidney is edema. "cough and dyspnea" refers to the condition of both water retention and yangming. When the patient falls into the hypochondrium, the patient may dyspnea with reversed flow of qi due to blood in the hypochondrium. "lung impediment, restlessness, dyspnea and vomiting; for heart impediment, there are obstructed vessels, restlessness leading to a bulging heart and sudden upward movement leading to dyspnea. "pathogenic factors attacking the collaterals of the hand yangming meridians and causing qi to fill the chest and dyspnea with branch amines. "it is the reverse of yang-brightness, which is an emotional sound when the patient cannot lie down. Yangming syncope, cough and dyspnea with fever, convulsions and epistaxis, hematemesis. "lung is small, it is less fluid, not sick and dyspnea; large lung usually indicates excessive fluid retention, so it is good at treating obstruction of qi in the chest and obstruction of qi in the throat. Cough with upper qi and shoulder rest due to high lung; it is good at treating hypochondriac pain because it is located under the lung and is close to the heart. The hard lung can not cause cough and dyspnea; a fragile lung may cause a bitter disease, and it is easy to be damaged. Lung end regularisation and difficult injury; a declined lung may also cause a pain in the chest. "pulmonary disease, dyspnea and cough, shoulder and back pain, sweating. "" the lung is congested, dyspnea but two months of fullness. "" pathogenic factors in the lung cause skin pain, asthma due to cold and heat, and sweating. Cough the shoulder and back. All herbs in this chapter are superior in all aspects. "it is due to the night when asthma comes out of the kidney, and causes the lung disease; if the liver is attacked by asthma due to abortion and terrorism, the spleen is harmed by pathogenic qi; the patient has a fear that asthma comes out of the lung and the heart is injured by the exogenous pathogenic qi; a sudden fall of water or dyspnea is caused by kidney and bone. When Fu is silent due to its life, the collaterals of the lung are reversed. "five zang-organs and six fu-organs all cause cough, and not only lung. "" this is all in the stomach, about the lungs. "

Cloud of Yi guan (medicine guan): "true Yuan consumption, dyspnea due to kidney qi rushing to … …, qi failing to return to Yuan". If the patient has kidney yang deficiency, unconsolidation of the lower primordial qi, kidney failure to dominate water, excessive water pathogen attacking the heart and attacking the lung, adverse rising of lung qi and asthma, the symptoms are shortness of breath, difficulty in continuous respiration, pale tongue with white coating, deep, thready or slow pulse. In traditional Chinese medicine, the occurrence and progression of asthma (bronchial asthma) are closely related to cold (including deficiency cold and excess cold).

The zhangzhongjing in the Han dynasty indicates that the fluid retention and turbid phlegm are related to the attack of asthma: for Shang Han Lun (treatise on Cold fever), Hou Po and Xin Zi Jia are added in the decoction of Gui Zhi; the syndrome of cough and upbeat disease pulse of lung abscess and the syndrome of phlegm-fluid retention disease pulse are marked by 'cough and upbeat, sound of chicken in throat', 'cough and upbeat', cough and upbeat, frequent spit and turbid, but insomnia. There are "phlegm in diaphragm, cough and dyspnea, cold and heat, back pain and low back pain, which appear by eye-selection, and it is marked by strong shaking and body-building and intermittent fluid retention". The proposed "phlegm-fluid drinker, when combining with warm herbs", is a big guideline for treating asthma clinically.

The Ming Dynasty Zhang Yue points out: asthma is persistent in the persistent root, which is caused by cold or fatigue, also known as asthma. The expression of "treatment of diseases due to vessels and asthma": is indicated for asthma caused by phlegm-fluid retention … … or exterior wind-cold affecting the muscle surface of the body. "

The Qing dynasty Lin pei Piano argues on the theory of class syndrome treatment and asthma syndrome treatment that the deficiency of the spleen and the kidney is caused by deficiency of the spleen and the kidney, and the frequent occurrence of asthma is caused by the introduction of wind and the lung channel; congenital deficiency, too sweet sour, and cold-attacked, and unreal phlegm-fluid retention, such as glue like lacquer, and nest like mortar, which adheres to the lung system, and makes a sound with qi pulsation in the respiratory system. "

The traditional Chinese medicine yang warming method is a main treatment principle for treating bronchial asthma, and the traditional Chinese medicine compound has obvious multi-target effect characteristics. Over the past decade, consumer interest in chinese medicine as a supplemental and replacement therapy has grown dramatically in western countries. According to the theory of traditional Chinese medicine, qi deficiency is one of the causes of the continuous attack of asthma, if qi deficiency is accompanied by wind phlegm stasis, the symptoms of asthma patients are difficult to control, and yang and asthma-relieving ointment aim at the pathogenesis. The traditional Chinese medicine compound based on the traditional Chinese medicine epidemic disease prevention theory and verified clinical curative effect is beneficial to supplementing a treatment scheme of asthma and brings a new medicine selection for patients.

Through research, the Yang and asthma relieving ointment has the functions of warming Yang, dispersing lung qi, dispelling cold, invigorating Yin and Yang, and strengthening vitality and consolidating the foundation of asthma lung and kidney deficiency. The effects of the traditional Chinese medicine are not only manifested in strengthening yang and cultivating vigor, dispelling cold and eliminating phlegm, relieving asthma and receiving qi; but also can regulate the immunologic function of the human body, warm yang, replenish essence, and strengthen healthy qi to eliminate pathogenic factors.

Compared with the similar products on the market, the Yang and asthma relieving ointment of the invention has the clinical advantages that:

yang-harmonizing asthma-relieving ointment has definite curative effect and safe medication. By monitoring three major routine, liver and kidney functions and electrocardiogram, no obvious abnormality is found, and no toxic or side effect is caused in clinical application.

Variety feasibility analysis:

tracheal asthma (asthma for short) is a heterogeneous clinical syndrome, is one of the most common chronic respiratory diseases, affects more than 3 hundred million people worldwide, and the number of asthma patients is gradually increased year by year. The WHO forecasts that 1 hundred million new patients suffering from asthma will happen in 2025, and asthma will bring a heavy burden to governments, families and patients in various countries. Since the concept of "asthma control" proposed by GINA in 2006, 2019 emphasized the therapeutic goals of "overall control" while reducing future risks of acute exacerbations, death, and the like. However, the asthma control rate in europe, asia-pacific countries and our country is far from reaching the GINA target, and some patients have great psychological conflict and poor compliance in receiving long-term treatment of GINA. More and more studies in recent years have shown that the addition of traditional Chinese medicines can reduce the dosage of control drugs (inhalation hormones) and even completely eliminate the need for long-term inhalation hormone therapy.

The Chinese patent medicine clinical application guideline-respiratory system disease book (2016 edition) can be used for treating asthma in the attack stage (with symptoms of time-out and obvious aura symptoms), and can be selected from Haizhu asthma relieving tablet, Suhuang cough relieving capsule and Zhichuanling oral liquid, and has the effects of dispelling wind, dispersing lung qi, relieving spasm, lowering qi and relieving asthma; however, the components contained in the Haizhu Chuanping tablet can cause great burden on the spleen and the stomach and cannot be taken for a long time, the Suhuang cough-relieving capsule has the main effects of treating dry and itching throat, repeated dry cough without phlegm, relieving cough and relieving sore throat and the like, and has not obvious effect on relieving asthma; for the treatment of asthma due to deficiency (short breath, dyspnea with movement, asthenia, and weak pulse), Chinese medicinal materials including SUZIJIANGQI pill, Gecko Capsule for relieving asthma, and CHUANZHI injection can be used. The gecko asthma-relieving capsule has the effects of nourishing yin, clearing away lung-heat, relieving cough and asthma; direct qi downward and resolve phlegm, warm kidney and receive qi. Can be used for treating adverse flow of qi, phlegm obstruction, cough, asthma, and stuffiness and fullness of the chest and diaphragm. The Suzi Jiangqi Wan is contraindicated for treating consumptive disease cough and asthma, short breath, fullness in chest, spontaneous sweating and night sweat caused by deficiency of both lung and kidney and lung heat due to yin deficiency, and red tongue without coating. It is not suitable for cough and dyspnea due to lung and kidney deficiency, and lung heat with phlegm dyspnea due to warm and dry nature.

Yang-nourishing and asthma-relieving ointment is used for patients with yang-deficiency type asthma, and yang-nourishing and compound prescription for replenishing essence, warming yang, dispelling cold and removing stagnation, which contains essence of yang-warming and cold-resisting method, and is especially suitable for patients with deficiency asthma/cold asthma with pathogenesis disorder. Antler glue has the effects of enriching blood and replenishing essence, tonifying kidney and supporting yang, tortoise-plastron glue has the effects of nourishing yin and suppressing yang, tonifying kidney and strengthening bone, turtle shell glue has the effects of nourishing yin and enriching blood, prepared rehmannia root has the effects of nourishing yin and enriching blood, replenishing essence and supplementing marrow, monkshood has the effects of dispelling cold and removing dampness, tonifying fire and supporting yang, negundo chastetree fruit has the effects of dispelling wind and relieving exterior syndrome and relieving cough and asthma, and the combination of monarch drug has the effects of warming yang and ventilating lung; raw astragalus, fried codonopsis pilosula, rhizoma curculiginis, herba epimedii, cocklebur fruit and spina gleditsiae are used as ministerial drugs, the codonopsis pilosula is used for tonifying qi and strengthening spleen, the astragalus is used for tonifying qi and consolidating superficial resistance to help the codonopsis pilosula to strengthen body resistance, the rhizoma curculiginis and the herba epimedii are used for tonifying kidney yang, warming spleen yang and strengthening bones and muscles, the cocklebur fruit has the effects of dispelling wind and removing dampness, and dredging orifices and relieving pain, the ministerial drugs are used for treating spleen yang, kidney yang and defensive yang simultaneously, and are used for strengthening and reinforcing yang and consolidating essence, dispelling cold and resolving phlegm, and the qi of triple energizer yang; the dried rehmannia root, nacre, dandelion, oldenlandia diffusa and gypsum are used as adjuvant drugs, the dried rehmannia root is used for clearing heat, promoting fluid production and nourishing yin, the nacre liver is used for suppressing yang hyperactivity, the liver is used for clearing liver heat, improving eyesight, calming heart and soothing nerves, the dandelion, the oldenlandia diffusa and the gypsum are used for clearing heat and removing toxicity, the adjuvant drugs on one hand counteract yang-supporting drugs easily cause the deficiency fire of heart and liver to be endogenous and phlegm to be phlegm-heat although the drugs are hot to be phlegm-heat, on the other hand, the asthma is used for controlling bad exogenous pathogenic factors to attack lung, the heat and cold are easily generated and toxic, the cold and the heat are opposite, the; the baked ginger charcoal and the prepared licorice root are used as guiding drugs to harmonize the other drugs and harmonize the middle energizer to dissipate phlegm-dampness, so as to astringe and astringe lung qi. The compatibility has the effects of warming yang and ventilating lung, strengthening body resistance and reinforcing primordial qi, and receiving qi and relieving asthma, starts with the basic pathogenesis of bronchial asthma, namely yang deficiency and internal phlegm stagnation, treats both symptoms and root causes, overcomes the defect that the Chinese patent medicine treats asthma, regulates and controls the unbalance state of the immune system of an asthma patient, improves the cellular immunity and airway defense function of the patient, and leads the patient to induce the repeated attack of asthma or the chronic continuous obvious reduction due to upper airway infection; has direct effects of relieving spasm and asthma, eliminating phlegm and resisting inflammation, and can directly improve clinical symptoms and airway inflammation state of patients, so that asthma can more easily reach the control target, and the control stability is improved.

Disclosure of Invention

The invention aims to provide a traditional Chinese medicine composition for effectively treating asthma aiming at the defects of the prior art.

In order to achieve the purpose, the invention adopts the technical scheme that:

firstly, the invention provides a traditional Chinese medicine composition for treating asthma, which comprises the following raw material medicines in parts by weight: 4-5 parts of tortoise-plastron glue, 4-5 parts of turtle shell glue, 2-4 parts of deerhorn glue, 5-7 parts of monkshood, 14-16 parts of negundo chastetree fruit, 8-10 parts of prepared rehmannia root, 5-7 parts of cocklebur fruit, 14-16 parts of raw astragalus root, 7-8 parts of fried codonopsis pilosula, 8-10 parts of epimedium herb, 5-7 parts of curculigo rhizome, 4-6 parts of spina gleditsiae, 14-16 parts of radix rehmanniae recen, 14-16 parts of mother of pearl, 14-16 parts of dandelion, 14-16 parts of oldenlandia diffusa, 7-8 parts of gypsum, 5-7 parts of baked ginger carbon and 4-5 parts of honey-fried licorice root.

Preferably, the traditional Chinese medicine composition consists of the following raw material medicines in parts by weight: 4.5 parts of tortoise-plastron glue, 4.5 parts of turtle shell glue, 3 parts of antler glue; 6 parts of monkshood, 15 parts of negundo chastetree fruit, 9 parts of prepared rehmannia root, 6 parts of cocklebur fruit, 15 parts of raw astragalus root, 7.5 parts of fried codonopsis pilosula, 9 parts of epimedium herb, 6 parts of curculigo orchioides, 4.5 parts of spina gleditsiae, 15 parts of radix rehmanniae recen, 15 parts of mother-of-pearl, 15 parts of dandelion, 15 parts of oldenlandia diffusa, 7.5 parts of gypsum, 6 parts of baked ginger carbon and 4.5 parts of honey-fried licorice root.

More preferably, the traditional Chinese medicine composition is prepared into a clinically acceptable pharmaceutical preparation according to a conventional traditional Chinese medicine preparation method, and the pharmaceutical preparation is granules, powder, capsules, tablets or oral liquid.

In addition, the invention also provides application of the traditional Chinese medicine composition in preparing a medicine for treating asthma.

Preferably, the asthma is yang-deficiency asthma.

More preferably, the asthma is rheumatoid blood stasis syndrome asthma caused by yang deficiency.

Yang and asthma relieving ointment is a preparation which is entrusted to external processing in our hospital. Through the observation of the curative effect and the safety of more than 100 patients with bronchial asthma, the patients have good response, no toxic or side effect is seen, and no similar products are supplied in the market. The main functions of the recipe are warming yang, ventilating lung, dispelling cold, consolidating constitution, promoting inspiration and relieving asthma. In the formula, antler glue, tortoise-plastron glue, turtle shell glue, prepared rehmannia root, monkshood and negundo chastetree fruit are used as monarch drugs, the antler glue enriches blood and benefits essence, tonifies kidney and strengthens yang, the tortoise-plastron glue enriches yin and subdues yang, the kidney and strengthens bone, the turtle shell glue enriches yin and enriches blood, the prepared rehmannia root enriches yin and nourishes blood, the monkshood dispels cold and removes dampness, supplements fire and strengthens yang, the negundo chastetree fruit dispels wind and relieves exterior syndrome, relieves cough and asthma, and the monarch drugs are used for warming yang, ventilating lung and dispelling cold, tonifying; raw astragalus, fried codonopsis pilosula, rhizoma curculiginis, herba epimedii, cocklebur fruit and spina gleditsiae are used as ministerial drugs, the codonopsis pilosula is used for tonifying qi and strengthening spleen, the astragalus is used for tonifying qi and consolidating superficial resistance to help the codonopsis pilosula to strengthen body resistance, the rhizoma curculiginis and the herba epimedii are used for tonifying kidney yang, warming spleen yang and strengthening bones and muscles, the cocklebur fruit has the effects of dispelling wind and removing dampness, and dredging orifices and relieving pain, the ministerial drugs are used for treating spleen yang, kidney yang and defensive yang simultaneously, and are used for strengthening and reinforcing yang and consolidating essence, dispelling cold and resolving phlegm, and the qi of triple energizer yang; the dried rehmannia root, nacre, dandelion, oldenlandia diffusa and gypsum are used as adjuvant drugs, the dried rehmannia root is used for clearing heat, promoting fluid production and nourishing yin, the nacre liver is used for suppressing yang hyperactivity, the liver is used for clearing liver heat, improving eyesight, calming heart and soothing nerves, the dandelion, the oldenlandia diffusa and the gypsum are used for clearing heat and removing toxicity, the adjuvant drugs on one hand counteract yang-supporting drugs easily cause the deficiency fire of heart and liver to be endogenous and phlegm to be phlegm-heat although the drugs are hot to be phlegm-heat, on the other hand, the asthma is used for controlling bad exogenous pathogenic factors to attack lung, the heat and cold are easily generated and toxic, the cold and the heat are opposite, the; the baked ginger charcoal and the prepared licorice root are used as guiding drugs to harmonize the other drugs and harmonize the middle energizer to dissipate phlegm-dampness, so as to astringe and astringe lung qi. The compatibility of the medicines can warm yang, promote lung and dispel cold to reduce phlegm, coordinate the exterior and interior, clear qi and remove toxicity and give consideration to both qi and yin. The combination of the above herbs can warm yang, resist cold and dispel phlegm.

The prescription source is as follows:

the syndrome of phlegm-fluid retention proposed in Shang Zhong Jing (treatise on Cold-induced diseases) of Han Dynasty is a large guideline for treating asthma clinically when warm herbs are combined. Qing, Wanghou, Wang hong dao (Collection of all raw materials from surgery) proposes that "Yanghe decoction" has the effects of warming Yang and enriching blood, dispelling cold and removing stagnation, and proposes "Yang He" rule. The latter-age medicine is widely used for treating various diseases with yang deficiency and cold accumulation syndrome by combining the thought of 'treating different diseases' of the traditional Chinese medicine based on the ability of warming yang, dispelling cold and removing stagnation and the syndrome differentiation of the traditional Chinese medicine. Modified and modified to form yang and dyspnea relieving ointment.

Source department:

lung disease research team/respiratory disease research institute of Longhua hospital

Clinical features of the department:

the Chinese and western medicine are combined to prevent and treat respiratory system diseases, and the important department characteristic of preventing and treating airway diseases (bronchial asthma, COPD, bronchiectasis and the like) by applying a yang warming and cold resisting method to treat the traditional Chinese medicine theory is highlighted.

Detailed description of the sources:

the formulation thinking of the prescription mainly comes from classic prescription of Yang He decoction and the viewpoint thereof published by the general Collection of surgery in the Qing & Wang Hongyou in 1740 years and the academic viewpoint of treating bronchial asthma which is firstly proposed by the subject team in the last 90 th century, based on which the lung disease subject team develops the relevant clinical practice, normative clinical research and basic research work around the treatment of the Yang warming therapeutic rule of traditional Chinese medicine for a long time, continuously focuses on the Yang He method in the prevention and treatment of chronic bronchial asthma (refractory asthma) and the optimization research of effective compound under the support of the scientific research projects of multiple natural and provincial levels, takes the meaning of Yang He on the basis of the classic compound Yang He decoction of Yang deficiency cold coagulation syndrome, develops the optimization research of long-term clinical practice, establishes the basic animal model and experimental platform of international research on target bronchial asthma in multiple dimensions, further based on lung/airway immune validation, respiratory dynamics and their molecular mechanism related series of intensive research works. Then, the multi-center RCT test of treating chronic persistent (refractory) bronchial asthma is carried out according to the international standard, the middle-term result shows better clinical curative effect, no obvious toxic or side reaction occurs, the project group evaluation can clearly and definitely solve the clinical problem, the formula is optimized and finished, and finally the Yang and asthma relieving ointment is formed.

The functional indications are as follows:

has effects of warming yang, dispersing lung qi, consolidating body constitution, invigorating qi, and relieving asthma, and can be used for treating asthma with yang deficiency.

The traditional Chinese medicine theory for adapting disease causes:

asthma belongs to the categories of asthma syndrome, phlegm and fluid retention, qi ascending and the like in the traditional Chinese medicine. The understanding of the pathological mechanism of the patients with symptoms (chronic duration and attack period) in traditional Chinese medicine and pharmacy mostly focuses on: deficiency (yang deficiency, qi deficiency), cold (deficiency cold, cold evil), wind (exowind, endogenous wind), phlegm, stasis and other five main pathological links, and there are also diseases between each link. The syndrome differentiation and type division of traditional Chinese medicine are divided into four main types of cold asthma, heat asthma, wind asthma, deficiency asthma and the like, wherein the heat asthma and the cold asthma belong to the syndrome characteristics of acute attack, and the wind asthma and the deficiency asthma are more suitable for the disease characteristics of chronic duration.

Pathogenesis of traditional Chinese medicine theory

The 'yang deficiency cold phlegm internal accumulation' is the basic pathogenesis of bronchial asthma, the 'yang warming and cold resistance phlegm elimination' is the main principle of the acute attack/chronic continuous treatment of the bronchial asthma, and the 'yang and asthma relieving ointment' is a formula for warming yang, ventilating lung, dispelling cold, tonifying yin and yang, and reinforcing primordial qi to consolidate the constitution, contains essence of the yang warming and cold resistance method, and is in conflict with the pathogenesis of asthma, particularly of asthmatic patients.

Therapeutic traditional Chinese medicine theory

The yang-harmonizing asthma-relieving ointment has the functions of warming yang, ventilating lung, dispelling cold, tonifying yin and yang, and consolidating the foundation of lung and kidney deficiency of asthma. Spleen yang, kidney yang and wei yang are treated simultaneously, ministerial drugs strongly assist monarch drugs in strengthening yang and consolidating vigor, dispelling cold and solidifying latent phlegm, and qi of yang heat of the three jiao is used for assisting deficiency of the primordial yang to recover. On one hand, contrarily-restraining yang-tonifying drugs are easy to cause deficiency fire of heart and liver to be endogenous and phlegm to be transformed into phlegm-heat although the drugs are hot, on the other hand, the countergoverning asthma is used for controlling poor exogenous pathogenic factors to attack lung and is easy to transform heat and generate toxicity, and the countergoverning cold and heat are more suitable for both the opposite formation, deficiency and excess and five internal organs, so that yang is helped to consolidate the constitution without retaining pathogenic factors.

Other theoretical bases are as follows: the current situation of pharmacological research of each medicine in the prescription

Medicinal deer horn glue

The antler glue has the effects of resisting inflammation, easing pain, activating blood, resisting hyperplasia of mammary glands, protecting gastric mucosa, resisting osteoporosis, activating blood, tonifying yang and the like^[1-5]。

The medicine flavor is as follows: tortoise plastron glue

The current research situation is as follows: is mainly used for nourishing yin and blood, stopping bleeding and enriching blood, tonifying kidney and strengthening bone, and the like, can promote cell proliferation, promote the proliferation of chondrocyte by regulating gene expression, and inhibit apoptosis^[6-7]。

The medicine flavor is as follows: turtle shell glue

The current research situation is as follows: carapax Trionycis has definite and reliable curative effect in improving immunity and resisting hepatic fibrosis and pulmonary fibrosis, but is used for treating fever due to yin deficiency, fatigue, hectic fever, endogenous deficient wind, amenorrhea, abdominal mass, etc. with carapax Trionycis in traditional Chinese medicine^[8]。

Medicinal prepared rehmannia root

Research on the effects of rehmanniae radix pharmacological function and activity in blood system, immune system, endocrine system, cardiovascular system and nervous system, tumor resistance, and aging resistance^[9]。

Radix Aconiti lateralis Preparata

Research status aconite contains alkaloids as main components, wherein C-19 type diterpenoid alkaloids with aconitine skeleton are used as main components, C-20 type diterpenoid alkaloids are used as secondary components, and marine alkaloid type, vitamin alkali type, naproxen type and delphinine type skeleton types are used as main components; contains flavone, saponin, ceramide, etc. in addition to alkaloid. The biological activity of radix Aconiti lateralis can be cardiotonic, anti-tumor, antiinflammatory, analgesic, immunity enhancing, and antiaging^[10]。

Medicinal negundo chastetree fruit

The research status has the functions of immunity enhancement, antipyretic analgesia, bacteriostasis, anticancer and anti-inflammation^[11]。

Medicinal astragalus root

The research status shows that the astragalus polysaccharide component can effectively improve the activity of macrophage of an organism, improve the functions of T cells and B cells, enhance the immunity of the organism and promote the recovery of the state of an illness; can also regulate and control the immune function of asthma patients; has effects in protecting liver, enhancing immunity, lowering blood pressure, lowering blood sugar and blood lipid, and resisting bacteria and tumor^[12]。

Medicinal codonopsis pilosula

Research status of Codonopsis pilosula extract on Escherichia coli and golden yellow in vitroHas obvious inhibiting effect on Staphylococcus chromogenes, Streptococcus and Salmonella, and has effects of enhancing immunity, resisting oxidation, relieving fatigue, protecting nerve, resisting bacteria, and resisting inflammation^[13]。

Medicinal herba Epimedii

At present, icariin is one of main active ingredients of epimedium herb, has the activities of immunoregulation, anti-inflammation, anti-aging, anti-tumor and the like, and can improve symptoms of various diseases such as osteoporosis, Alzheimer disease, Parkinson, cerebral ischemia, atherosclerosis, rheumatism and the like. The pharmacological activity of the compound comprises: promoting the generation and activation of osteoblasts, inhibiting the formation and function of osteoclasts and relieving osteoporosis; inhibiting the production of beta-amyloid, hyperphosphorylation of tau protein and reduction of dopamine content to protect the nervous system; protecting cardiovascular system by protecting cardiomyocytes, increasing cardiomyocyte number, improving endothelial dysfunction; promoting the function of reproductive organs; modulation of the immune system by modulation of T cell balance^[14]。

Medicinal curculigo orchioides

The current research shows that the curculigo orchioides has the effects of dissipating carbuncle swelling, strengthening bones and muscles, expelling cold and dampness, tonifying kidney yang, benefiting essence and blood and the like, and the modern pharmacological research shows that the curculigo orchioides has the activities of resisting oxidation, regulating immunity, resisting osteoporosis, tonifying kidney and strengthening yang, protecting liver, protecting nerves and the like^[15]。

Fructus Xanthii with medicinal flavor

The fructus xanthil as a traditional Chinese medicine mainly contains various chemical components such as volatile oil, fatty acid, phenolic acid, lignans, sesquiterpene lactone, thiazine diketone heterocycle and the like, and has pharmacological effects of resisting inflammation, easing pain, resisting bacteria, resisting viruses, reducing blood sugar, reducing blood fat, resisting tumors and the like^[16]。

Chinese honeylocust spine with medicinal flavor

The modern researches show that the spina gleditsiae mainly contains triterpenes, saponins, flavones, phenolic acids, echinocystic acid glucoside, coumarins and other chemical components, and has the effects of inhibiting bacteria, resisting viruses, improving immunity, resisting oxidation, resisting tumors, resisting coagulation, inhibiting thrombosis and inhibiting venous bloodThe proliferation of endothelial cells and the like also has influence on cardiovascular and cerebrovascular diseases^[17]。

Medicinal raw rehmannia root

Research status rehmannia root polysaccharide can enhance the immune function of the body^[18]It is mainly manifested in promoting the growth of immune organs and the proliferation and differentiation of normal lymphocytes, enhancing the phagocytic function of macrophages, stimulating the generation and release of cytokines, etc.

Medicinal dandelion

The research status has the functions of bacteriostasis, anti-inflammation, antioxidation, gastrointestinal tract protection and the like^[18]. The dandelion has broad-spectrum antibacterial effect, and has different degrees of inhibition effects on various pathogenic microorganisms such as gram-positive bacteria, gram-negative bacteria, fungi, spirochetes and the like. The dandelion has good effect and safety in treating acute mastitis, ulcerative colitis and acute suppurative tonsillitis in lactation.

Medicinal nacre

The research status shows that the pharmacological effects of the mother-of-pearl mainly include sedation, oxidation resistance, acute liver injury resistance, gastric acid neutralization and immunity regulation^[19]。

Herb of spreading Hedyotis

The spreading hedyotis herb is an annual hairy-fiber-free spreading herbaceous plant, can inhibit bacteria such as pneumococcus, staphylococcus aureus, dysentery bacillus and the like, has the effect of enhancing the immunity of the organism, and is an rare 'good medicine'^[20]。

Medicinal raw gypsum

The research status has the effects of fever abatement, immunoregulation, antivirus and the like^[6]. Gypsum Fibrosum can inhibit excessive exciting body temperature center during fever, and has strong and rapid antipyretic effect; can regulate the balance of T lymphocytes; increasing the phagocytic capacity of rabbit alveolar macrophages on staphylococcus albus and colloidal gold; interaction with nucleic acids renders the body virus-free.

Medicinal licorice root

The research status has the pharmacological actions of resisting bacteria, oxidation and inflammation, regulating immunity, resisting ulcer, detoxifying, resisting cancer, resisting hepatic fibrosis and the like^[20]。

The prescription is used in the medical institution

The service life of the product in the medical institution is 7 years (10 months in 2013 to 8 months in 2020)

Description of the specific embodiments

The idea of formulation of the prescription mainly comes from classic prescription of Yang Hetang in the Collection of the general health of surgery and the viewpoint thereof published by Qing & Wang Honghou in 1740 years, and the academic viewpoint of treating bronchial asthma by 'warming Yang and cold-resisting method' proposed by professor Wu Yin root of the ancestor of the subject team in the last 90 th century, the research and development team develops the series clinical and basic research of 'warming Yang and cold-resisting method' for treating bronchial asthma for more than 20 years, and forms 'warming Yang and cold-resisting mixture' of the preparation in the hospital, thereby establishing the treatment principle of warming Yang, resisting cold and eliminating phlegm, and preliminarily formulating Yang and relieving asthma. The yang-warming and cold-resisting mixture (prepared common monkshood daughter root, baical skullcap root, peach seed, roasted ephedra each 10g, manchurian wildginger 5g, saxifrage 3g, centipede 2 and scorpion 3g) is prepared by adding materials on the basis of ephedra, mankshood and manchurian wildginger decoction, (1) the mixture is mainly used for treating acute attack stage of asthma, the traditional Chinese medicine distinguishes cold asthma, (2) no GINA (general information for treating asthma) guide for asthma is available in the research and development stage, the problem is different from the current stage, (3) the composition is obviously different from yang-relieving and asthma-relieving ointment, the yang-warming and cold-resisting mixture is prepared from mankshood, baical skullcap root, peach seed, roasted ephedra, manchurian wildginger, saxifrage; "Wuyingen professor treating bronchial asthma clinical experience summarization" treating asthma is mainly based on cough and asthma six-ingredient mixture (prepared aconite root, baikal skullcap root, peach kernel, prepared ephedra herb, asarum herb, saxifrage) and asthma-relieving capsule (epimedium, morinda root and cnidium fruit) formed on the basis of Zhongjing ephedra herb, prepared aconite root and asarum herb decoction, and morinda root of asthma-relieving capsule is used for treating patients in stable period with simple kidney-yang deficiency; yang and asthma relieving paste is based on the 'Yang and' viewpoint of Qing, Wanghou and the clinical experience of a lung disease research team for many years, and the 'Yin and Yang simultaneous treatment and Qi and blood tonifying' method is used for treating chronic duration deficiency asthma according to the respiratory disease division asthma group of the Chinese medical society, the bronchial asthma control guideline (2016 edition) is used for the treatment of the bronchial asthma division syndrome, and the control incomplete asthma patient → reduction of ICS dosage and side effect reduction → disuse is combined with ICS to treat the global bronchial asthma control initiative (GINA). The prior art of the prescription of the patent does not disclose relevant contents. In 7 years between 10 and 8 months in 2013, lung disease research teams of the hospital successively undertake a plurality of projects of traditional Chinese medicine for preventing and treating airway diseases, clinical research and basic research of a plurality of yang and asthma-relieving compound medicines for treating deficiency-cold cough and asthma, chronic persistent deficiency asthma and obesity asthma are successively carried out in the process of promoting implementation of the projects, clinical data and basic research data of a certain sample amount are accumulated, and a foundation is laid for clinical application and popularization of yang and asthma-relieving ointment. The details are as follows.

In 2013, in 10 months, the team undertakes the optimized research of a characteristic diagnosis and treatment scheme of Kewei project (13401905400) -deficiency-cold cough and asthma 'winter disease cured in summer' in Shanghai. The clinical observation and research of small samples of yang and compound treatment of bronchial asthma are carried out preliminarily, the total is more than 100 cases, and data analysis shows that the treatment of bronchial asthma by the yang warming and cold resisting method has certain curative effect in the aspects of improving clinical symptoms and the like.

In 2016, 10 months, a team starts to be responsible for promoting the research of the immune regulation mechanism of Yang and Tang plus and minus on patients with chronic persistent asthmatics (LYTD-36(D36)), and in 2016, 9 months to 2019, the small sample clinical observation research of Yang and Zhichuang compound treatment of bronchial asthma is developed, more than 90 cases of bronchial asthma are brought into, the relation between the cellular immune condition of the patients and the change of the microbial colonies of the airways is researched by collecting the peripheral blood of the patients before and after treatment and the induced sputum sample, so that the research and solution method is provided for the research of the concept of 'Yang and Tang' plus and minus on the regulation effect mechanism of the microbes in the airways of the patients with chronic persistent asthmatics and the possible immune mechanism of the patients with chronic persistent asthmatics, the clinical treatment and research concept of intractable asthma are widened, and the research value is better.

In 11 months in 2017, a team is responsible for promoting the development of a Haishinkang Hospital development center project (SHDC12017118) -a research project of a Chinese and Western medicine combined treatment bronchial asthma (chronic persistence) diagnosis scheme, and the clinical observation of Yang and asthma-relieving compound treatment bronchial asthma and a protocol prescription (9 months in 2017-9 months in 2020) are completed in 80 cases of clinical observation of Yang and asthma-relieving treatment bronchial asthma by using multiple cooperation units (Yueyang Chinese and Western medicine combined hospital affiliated to Shanghai medicine university, Fudan university affiliated to Zhongshan hospital, and the like). The preliminary research results show that the curative effect of the compound therapy of yang and relieving asthma on bronchial asthma is exact, and the safety is higher.

In 2019, in 9 months, based on the early stage research foundation, the team undertakes the capability construction of the national traditional Chinese medicine administration project-traditional Chinese medicine evidence-based medical research center in Longhua hospital, based on the popularization of the syndrome-based medical concept of traditional Chinese medicine, the special disease of the Longhua hospital is taken as the entry point, under the guidance of the theory of traditional Chinese medicine, a system for clinical research design, evaluation technical specification and quality assurance of evidence-based traditional Chinese medicine is constructed and perfected, by strengthening the construction of talent teams, informationized construction and developing multi-center and large-sample random contrast clinical test projects of characteristic disease species, starting from chronic persistent asthma which is difficult to control clinically, and adopting a means of combining Chinese and western medicine, by developing RCT clinical research, the curative effect characteristics and the safety of the traditional Chinese medicine in the aspect of improving the control rate of chronic persistent asthma are further determined, and a traditional Chinese medicine scheme/compound recipe with high quality evidence support is provided for the prevention and treatment of asthma; meanwhile, the regulation characteristics of the traditional Chinese medicine on the whole cellular immunity and the local airway microbial environment of the patient are researched exploratory, and more theoretical basis and clinical thought are provided for the traditional Chinese medicine to treat chronic persistent asthma. And the construction of clinical research capacity of the clinical research center of Longhua hospital is further promoted, a special talent team which has evidence-based medical thought and capacity and higher level and can carry out high-level clinical experiment design and organization is cultivated, and a standard and precise and technically-advanced evidence research and evaluation technology platform of traditional Chinese medicine evidence is formed.

The invention has the advantages that:

aiming at the etiology and pathology of the asthma caused by the syndrome of yang deficiency, rheumatism and blood stasis, the raw material medicines and the proportion of the raw material medicines are optimized, the curative effect is obvious, no toxic or side effect exists, and the curative effect is obvious for some intractable asthma patients. The medicines in the formula have synergistic effect, and the formula accords with compatibility of monarch, minister, assistant and guide, has the effects of warming yang, ventilating lung, dispelling cold, tonifying yin and yang, and consolidating the lung and kidney deficiency of asthma, can regulate the immunologic function of a human body, warm yang, replenish essence, and support vital qi to help eliminate pathogenic factors, brings new medicine selection for patients, and has good application prospect.

Drawings

Figure 1 is a schematic diagram of animal modeling and drug intervention.

FIG. 2 shows the changes in airway resistance and lung compliance in groups of mice following gradient methacholine challenge (Mean + -SE, n-6),^*P＜0.05；AS VS AT,^#P＜0.05。

FIGS. 3-5 are the white blood cells from the lung tissue of each group of mice and the differential flow analysis chart.

FIG. 6 shows HE staining results (200 μm) of lung tissues of mice in each group.

FIG. 7 shows that the 2016 group, month 1, undertakes the youth fund (81503508) which is the subject of national science fund, formally starts the mechanism research of bronchial asthma, initially searches for the mechanism of yang and compound treatment of asthma, and finds that the levels of CalcamRNA, IL-5 and IL-17 in lung tissues of asthmatic mice are higher than those of healthy mice, and the levels of CalcamRNA, IL-5 and IL-17 are obviously reduced after yang harmonizing decoction treatment. (Calca mRNA encodes CGRP mainly)

Fig. 8 shows that in month 1 in 2020, based on the national theme born in 2016, the foundation (81973817) on the basis of the national foundation of natural science is further born, and the research on the regulation and control mechanism of the yang and the prescription on the regional immune network of the asthmatic mouse through the synergistic activation of the PNECs/ILCs finds that in the OVA-induced allergic asthma mouse model, the yang and the prescription can obviously reduce the infiltration of inflammatory cells such as EOS, lymphocytes and macrophages in alveolar lavage fluid and reduce the number of ILC2 cells in lung tissues.

Detailed Description

The invention will be further illustrated with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Furthermore, it should be understood that various changes and modifications can be made by those skilled in the art after reading the disclosure of the present invention, and equivalents fall within the scope of the appended claims.

EXAMPLE 1 Chinese medicinal composition 1

The raw material medicaments are taken according to the following weight portion:

4 parts of tortoise-plastron glue, 4 parts of turtle shell glue, 2 parts of deerhorn glue, 5 parts of monkshood, 14 parts of negundo chastetree fruit, 8 parts of prepared rehmannia root, 5 parts of cocklebur fruit, 14 parts of raw astragalus root, 7 parts of fried codonopsis pilosula, 8 parts of epimedium herb, 5 parts of curculigo orchioides, 4 parts of spina gleditsiae, 14 parts of raw rehmannia root, 14 parts of mother of pearl, 14 parts of dandelion, 14 parts of oldenlandia diffusa, 7 parts of gypsum, 5 parts of baked ginger carbon and 4 parts of honey-fried licorice.

EXAMPLE 2 Chinese medicinal composition (II)

5 parts of tortoise-plastron glue, 5 parts of turtle shell glue, 4 parts of deerhorn glue, 7 parts of monkshood, 16 parts of negundo chastetree fruit, 10 parts of prepared rehmannia root, 7 parts of cocklebur fruit, 16 parts of raw astragalus root, 8 parts of fried codonopsis pilosula, 10 parts of epimedium herb, 7 parts of curculigo orchioides, 6 parts of spina gleditsiae, 16 parts of raw rehmannia root, 16 parts of mother of pearl, 16 parts of dandelion, 16 parts of oldenlandia diffusa, 8 parts of gypsum, 7 parts of baked ginger carbon and 5 parts of honey-fried licorice.

EXAMPLE 3 Chinese medicinal composition (III)

4 parts of tortoise-plastron glue, 5 parts of turtle shell glue, 2 parts of deerhorn glue, 7 parts of monkshood, 14 parts of negundo chastetree fruit, 10 parts of prepared rehmannia root, 5 parts of cocklebur fruit, 16 parts of raw astragalus root, 7 parts of fried codonopsis pilosula, 10 parts of epimedium herb, 5 parts of curculigo orchioides, 6 parts of spina gleditsiae, 14 parts of raw rehmannia root, 16 parts of mother-of-pearl, 14 parts of dandelion, 16 parts of oldenlandia diffusa, 7 parts of gypsum, 7 parts of baked ginger carbon and 4 parts of honey-.

EXAMPLE 4 Chinese medicinal composition (IV)

5 parts of tortoise-plastron glue, 4 parts of turtle shell glue, 4 parts of deerhorn glue, 5 parts of monkshood, 16 parts of negundo chastetree fruit, 8 parts of prepared rehmannia root, 7 parts of cocklebur fruit, 14 parts of raw astragalus root, 8 parts of fried codonopsis pilosula, 8 parts of epimedium herb, 7 parts of curculigo orchioides, 4 parts of spina gleditsiae, 16 parts of raw rehmannia root, 14 parts of mother of pearl, 16 parts of dandelion, 14 parts of oldenlandia diffusa, 8 parts of gypsum, 5 parts of baked ginger carbon and 5 parts of honey-fried licorice.

EXAMPLE 5 Chinese medicinal composition (V)

4.5 parts of tortoise-plastron glue, 4.5 parts of turtle shell glue, 3 parts of antler glue; 6 parts of monkshood, 15 parts of negundo chastetree fruit, 9 parts of prepared rehmannia root, 6 parts of cocklebur fruit, 15 parts of raw astragalus root, 7.5 parts of fried codonopsis pilosula, 9 parts of epimedium herb, 6 parts of curculigo orchioides, 4.5 parts of spina gleditsiae, 15 parts of radix rehmanniae recen, 15 parts of mother-of-pearl, 15 parts of dandelion, 15 parts of oldenlandia diffusa, 7.5 parts of gypsum, 6 parts of baked ginger carbon and 4.5 parts of honey-fried licorice root.

Example 6 paste

The preparation method comprises the following steps:

the raw material medicaments are taken according to the weight part ratio of the embodiment 1-5 respectively, water is added for decocting for 1-2 hours, filtering is carried out, the filtrate is concentrated, the supernatant is cooled to the room temperature, water is added, stirring is carried out, standing is carried out, and the supernatant is concentrated into clear paste.

Example 7 granules

The preparation method comprises the following steps:

the raw material medicaments are taken according to the weight part ratio of the embodiment 1-5 respectively, water is added for decocting for 1-2 hours, the filtration is carried out, the filtrate is concentrated, the supernatant is cooled to the room temperature, the water is added, the stirring and the standing are carried out, the supernatant is concentrated into clear paste, and then the conventional auxiliary agent of the granules is added.

Example 8 tablets/capsules

The preparation method comprises the following steps:

the raw materials are taken according to the weight part ratio of the embodiments 1-5 respectively, water is added for decocting for 1-2 hours, filtering is carried out, the filtrate is concentrated, the temperature is cooled to the room temperature, the supernatant is concentrated, water is added, stirring and standing are carried out, the supernatant is concentrated into clear paste, and then the conventional auxiliary materials of tablets/capsules are added.

Example 9 clinical trial

Data and method

1. Data source

Clinical observation research of yang and compound treatment of bronchial asthma, which is carried out by the affiliated Longhua hospital of Shanghai medical university in 2016, 9 months to 2019, 9 months, is collected.

2. Diagnostic criteria^[21]

Clinical symptoms and signs of typical asthma: (1) recurrent wheezing, shortness of breath, with or without chest distress or cough, frequent nocturnal and morning episodes often associated with exposure to allergens, cold air, physical and chemical irritations, as well as upper respiratory infections, exercise, etc.; (2) during attack, the two lungs can hear the wheeze sound scattered or diffused, and the expiratory phase is prolonged; (3) the symptoms and signs can be therapeutically or spontaneously alleviated.

Objective examination of variable airflow restriction: (1) positive in bronchodilator test (> 12% increase in FEV1 and >200m1 increase in FEV1 absolute after bronchodilator inhalation); (2) positive bronchial excitation test; (3) peak Expiratory Flow (PEF) mean diurnal variability (7 d consecutive, sum of daily PEF diurnal variability/7) > 10%, or peri-PEF variability { (highest PEF value-lowest PEF value in 2 weeks)/[ (highest PEF value + lowest PEF value in 2 weeks) × 1/2] × 100% } > 20%.

The compound preparation meets the symptoms and signs, has any one of objective examination of airflow limitation, and can be used for diagnosing asthma except wheezing, short breath, chest distress and cough caused by other diseases.

3. Inclusion criteria

Firstly, the age is 15-75 years;

② patients with chronic persistent asthma can be diagnosed;

③ the period of uncontrolled asthma symptoms is more than 3 months per year;

after informed, the study was voluntarily participated in and signed an informed consent.

4. Exclusion criteria

(ii) combining significant upper/lower respiratory tract infections (viruses/bacteria) within 4 weeks;

② oral/intravenous glucocorticoid treatment for 4 weeks or long-term continuous/intermittent;

③ using antibacterial medicine for 4 weeks;

fourthly, history of lethal asthma attack;

fifthly, patients with clearly diagnosed emphysema, tuberculosis, sarcoidosis, pulmonary fibrosis, lung cancer and the like;

sixthly, the patient has serious heart diseases, including: (1) angina pectoris; (2) myocardial infarction; (3) heart failure; (4) any other heart disease or the like judged by the investigator to be unsuitable for participation in the trial;

seventhly, the history of liver and kidney dysfunction or serious primary diseases of the liver and the kidney;

eighthly, history of serious primary diseases of hematopoietic system;

ninthly, there is a history of immunodeficiency (including but not limited to positive HIV detection, or other acquired, congenital immunodeficiency disease, or there is a history of organ transplantation);

r in combination with other investigators to determine diseases that may affect the clinical presentation of the study, or increase the risk of the study;

patients who have participated in other drug clinical trials or taken other study drugs within nearly 4 weeks;

those with known history of allergy to the present pharmaceutical composition;

history of smoking;

contraindications with sampling modalities;

the investigator judged that the test could not be completed.

5. Medication regimen

Patients will be randomly assigned to the traditional Chinese medicine treatment group or the placebo group, and subjects will take oral trial medication or placebo once a day, morning and evening, for 4 weeks (28 days) of intervention. Prior to enrollment, all subjects will receive or maintain relevant baseline therapy, including inhalation of glucocorticoids (ICS) or Beta2 receptor agonists, etc., based on a comprehensive assessment by a lung disease investigator.

The yang harmonization group participants will receive twice daily flavored yang harmonization granules or placebo granules, 9.25g each time, for 4 weeks, all by 100 ml of boiling water for breakfast and supper.

6. Observation index

(1) The safety index is as follows: ICS, Beta2 receptor agonist, positive and compound adverse reactions are dynamically monitored by blood routine, liver and kidney functions, electrolytes, CRP, myocardial infarction zymogram and the like;

(2) the curative effect index is as follows:

ACT index: the primary assessment of asthma improvement in clinical patients was the ACT score used to assess the clinical efficacy of the modified yang decoction and placebo groups in the management of asthma after 28 days of intervention.

Lung function index: including FEV1 improvement rate, FVC improvement rate.

Second, result in

2.1 Baseline data for Inclusion cases

In the study, 101 patients are screened from 7 months in 2017 to 9 months in 2019, 37 patients are excluded from the study, 20 patients do not accord with the inclusion exclusion standard, and finally 44 patients are used as volunteers to participate in the clinical study. 44 of these were randomized, 24 of them were assigned to the test drug group and 20 were the control drug group. Wherein 23 people in the traditional Chinese medicine group complete one-month drug intervention, and 19 people in the placebo group complete one-month drug intervention. 1 person in the traditional Chinese medicine group and the placebo group stops taking the medicine by self, and other people do not find the adjustment of the medicine taking dosage. The baseline condition of the subjects was balanced in the two groups with respect to age, gender, height, weight, BMI, diabetes, hormone usage and hypertension, with no significant difference.

The test period curative effect evaluation indexes of the test mainly concern the following 3 indexes: the change in ACT score from baseline, the rate of change in forced expiratory volume in one second (FEV1) from baseline, and the rate of change in Forced Vital Capacity (FVC) from baseline. Baseline ACT scores and lung function indices are shown in table 1, and no statistical difference was seen between the two groups (see table 1).

TABLE 1 Baseline ACT and Lung function status

Difference comparison is based on Wilcoxon rank sum test

*-P<0.05

2.2 Primary clinical endpoints

The covariance showed that the mean traditional Chinese medicine ACT score was 3.484 points higher than the placebo group, and at the test level of 0.05, the differences in ACT improvement between the two groups were considered statistically different. And the secondary indexes comprise that the FVC traditional Chinese medicine is improved by 2.417 percent compared with a placebo group, and the FEV1 traditional Chinese medicine is improved by 3.979 percent compared with the placebo group. Compared with a placebo group, the FEV1/FVC traditional Chinese medicine group is increased by 2.209%, the PEF traditional Chinese medicine group is increased by 4.555%, and the FeNO (Fractional ExhaledNitric oxide) traditional Chinese medicine group is increased by 16.63(ppb) compared with the placebo group. Other indicators showed a trend of improvement, but did not show statistical differences.

Table 2 curative effect index covariance analysis results

Third, conclusion

In this randomized double-blind placebo-controlled clinical study, the baseline profile was balanced between the two groups of subjects. Subject compliance was good, and only 2 persons (4.5%) did not receive treatment for the entire 4 weeks. Adverse events that may be related, positively related, or not adjudicated for treatment were not seen. In the test, the ratio of the basic treatment regimens in the two groups was relatively balanced, and no significant change was observed in the basic treatment regimens during the test, so the effect of the basic treatment on the change in therapeutic effect was considered comparable in the two groups. After receiving 4 weeks of treatment, the traditional Chinese medicine group showed a significant increase in ACT score of 3.484 points (1.549,5.418) over the placebo group. The secondary index, namely the relative improvement of the FVC traditional Chinese medicine group by 2.417% (-3.020,7.859) and the relative improvement of the FEV1 by 3.979% (-2.650,10.610), has no obvious statistical difference. Based on the ACT index, we reasoned that yang and asthma-relieving fuf plus basal therapy is effective and safe for asthma management and treatment, and it is hopeful to be a good solution in the asthma management and management segment. The secondary index FEV1 and FVC, although not showing statistical differences, showed an increased trend for the yang and asthma-relieving compound compared to the placebo group.

Example 10 basic Experimental study of Yang and Ding Chuan Fang for treating asthma

Data and method

1. Preparation of Experimental drugs

The yang and the compound are prepared into paste, dissolved, mixed evenly and administrated according to the weight of 0.2ml/20 g. The concentration of the decoction is converted according to the daily dose of an adult (refer to a pharmacological experimental method, the surface area ratio of an animal body is converted into an equivalent dose, namely the dose of a mouse medicament is multiplied by 9.1 times of the dose of a human medicament).

2. Establishment of animal model

Healthy female BALB/c mice 18, SPF grade, 6-8 weeks old, after 1 week of acclimatization. Mice were administered 100ul of sensitizing solution (OVA + PBS 2mg/ml, and alum diluted to 1mg/ml, such as 10mg OVA +5ml PBS +5ml alum) by intraperitoneal injection on day 0 and day 7, respectively; on days 14-23, 3% OVA was given for nebulization 1 time every other day for a total of 5 nebulizations. Day 24-26 for 3 consecutive days, mice were anesthetized with ether daily and then given a nasal drop of 50ul of 1mg/ml OVA (50ug) 1 time a day, measured after 28 days of anesthesia (see FIG. 1).

3. Animal grouping and drug intervention

18 mice were randomly divided into 3 groups of 6 mice each. The specific grouping is as follows: the blank control group and the asthma model group are all treated by the traditional Chinese medicine treatment group by the traditional Chinese medicine gavage from the 14 th day, and the control group is treated by the normal saline gavage 1 time a day, 0.2ml each time and 14 days continuously. The animals were sacrificed on day 28 and the material was harvested (see FIG. 1).

3. Evaluation:

and (3) respiratory function detection: after all animals were anesthetized on day 28, the trachea was exposed, a transverse incision was made, the trachea was intubated and placed in a stereographic box, and airway hyperreactivity and lung compliance were measured under gradient challenge with methacholine using a Buxco invasive RC respiratory function measuring instrument.

Counting inflammatory cells: after the respiratory function is detected, the eyeball is picked and blood is collected, a self-made sterile alveolar lavage tube is inserted into the trachea of the mouse and is tied by silk thread, and lung tissues are taken for digestion, homogenate and extraction. The cell pellet cells were resuspended in 0.1ml PBS containing 1% BSA and sorted for BALF white blood cell counts using a MINDRAYBC-5300vet five-sorting animal hemocytometer.

Pathological organization of lung tissue: the collected posterior lobe of the right lung is fixed in 10% neutral formalin solution for 1 week, and then taken out, and the water in the tissue mass is removed by using low-concentration to high-concentration alcohol (75% alcohol-85% alcohol-95% alcohol-100% alcohol) as a dehydrating agent in sequence. And taking out the tissue block, putting the tissue block in xylene until the tissue block is transparent, and replacing alcohol in the tissue block. And (3) placing the transparent tissue block into melted paraffin, placing the transparent tissue block and the melted paraffin into a paraffin dissolving box for heat preservation, and embedding after the paraffin is completely immersed into the tissue block. Fixing the embedded wax block in a slicer, cutting into slices with thickness of 5 μm, ironing the cut slices in hot water, sticking onto a glass slide, placing in a thermostat at 45 deg.C, and oven drying. Removing paraffin from the slices by xylene, sequentially removing water from high-concentration alcohol to low-concentration alcohol, and hydrating in distilled water. Staining with hematoxylin for 5min, washing with tap water, air drying, and differentiating with hydrochloric acid ethanol for 30sec, wherein the time for extraction and insertion is several times. Washing under flowing water for 30min, and adding distilled water for 3-5 min. Taking out, sequentially soaking in 70% and 90% alcohol, and dehydrating for 10 min. Taking out, placing into eosin dye solution, dyeing for 3min, and dehydrating with anhydrous ethanol for 2min for 2 times. Then, xylene was added for 10min to make the sections transparent. Finally, the transparent section is dripped with neutral gum, covered with a cover glass, sealed and labeled. And (3) using an 80I fluorescence phase contrast positive microscope to magnify by 200 times in a bright field, observing HE stained sections of mouse lung tissues, and selecting representative lung tissue structures for shooting.

4. Statistical analysis

Metrology data is expressed as mean + -SEM. And (4) comparing the two groups to perform a homogeneity test of variance, wherein the normal distribution adopts an independent sample t test, and the non-normal distribution adopts a Mann-Whitney nonparametric test. And performing multi-group comparison by adopting One-Way ANOVA (One-Way ANOVA), performing multiple comparison on the mean of a plurality of samples, performing LSD (least squares) test on all variances, and performing Games-Howell test on all variances. P < 0.05 was considered statistically different.

Second, result in

And (3) a respiratory function detection result: after different concentrations of acetylcholine are excited, the model group mice have obvious increase of airway resistance, the 3 doses are statistically different from the normal group, the airway resistance is reduced after the traditional Chinese medicine treatment, and the treatment group is only statistically different from the blank group in high dose (figure 2): the lung compliance of the mice in the asthma model group is obviously reduced, and the mice have statistical difference (P is less than 0.05) compared with the normal group in three doses of 3.125, 6.25 and 12.5; after treatment with traditional Chinese medicines, the lung compliance of asthmatic mice is improved, and the high dose is statistically different from that of a model group (which indicates that Blank is a Blank control group, AS is a disease model group, and AT is a traditional Chinese medicine group).

Counting inflammatory cells: it was found (Table 3 and FIGS. 3-5) that the number of leukocytes in the lung of the mice in the model group was significantly increased compared to the number of leukocytes in the lungs of the mice in the blank group, and the total number of leukocytes and the differential count were statistically different, and the number of leukocytes in the asthmatic mice was decreased after the treatment with the Chinese medicine. The eosinophils of the mice in the Model group are obviously increased, and the total leukocytes, lymphocytes and eosinophils of the lungs of the mice with asthma after the treatment of the traditional Chinese medicine are all reduced, and have statistical differences (which indicates that Blank is a Blank control group, Model is a disease Model group, and YH is a positive and antiasthmatic cream group).

TABLE 3 white blood cells in the Lung tissue of mice in each group and their differential counts

Note: (Mean ± SE, n ═ 6), to Blank ratio P < 0.05, P < 0.01; ratio to Model^#P＜0.05，^##P＜0.01。

Pathological results of lung tissue: lung tissue from each group of mice was collected and HE stained and observed under light (200 μm) (fig. 2): the normal group of mice has clear bronchus and alveolus structures, smooth alveolar walls and normal bronchus shapes; the model group mice have the pathological manifestations of obvious inflammatory cell infiltration, epithelial cell hyperplasia, airway wall thickening and the like; after treatment with traditional Chinese medicines, the asthma mice had improved inflammatory cell infiltration degree compared with the Model group, and the alveolar and bronchial structures tended to be normal (indicating Blank control group, Model group, and YH group).

The research shows that the Yang and the compound recipe have obvious curative effect on the clinical treatment of the bronchial asthma, and the observation of the influence of the Yang and the compound recipe on the intervention of an asthmatic mouse also shows that the Yang and the compound recipe can improve the airway hyperresponsiveness of the asthmatic mouse, reduce the number of inflammatory cells in the lung, and simultaneously improve the pathological inflammatory cell infiltration of lung and alveolar tissues, the airway remodeling and the mucous membrane hyperplasia, thereby proving that the Yang and the compound recipe are the asthma treatment prescription with great potential.

Reference to the literature

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The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and additions can be made without departing from the principle of the present invention, and these should also be considered as the protection scope of the present invention.

Claims

1. The traditional Chinese medicine composition for treating asthma is characterized by comprising the following raw material medicines in parts by weight: 4-5 parts of tortoise-plastron glue, 4-5 parts of turtle shell glue, 2-4 parts of deerhorn glue, 5-7 parts of monkshood, 14-16 parts of negundo chastetree fruit, 8-10 parts of prepared rehmannia root, 5-7 parts of cocklebur fruit, 14-16 parts of raw astragalus root, 7-8 parts of fried codonopsis pilosula, 8-10 parts of epimedium herb, 5-7 parts of curculigo rhizome, 4-6 parts of spina gleditsiae, 14-16 parts of radix rehmanniae recen, 14-16 parts of mother of pearl, 14-16 parts of dandelion, 14-16 parts of oldenlandia diffusa, 7-8 parts of gypsum, 5-7 parts of baked ginger carbon and 4-5 parts of honey-fried licorice root.

2. The traditional Chinese medicine composition according to claim 1, which is prepared from the following raw materials in parts by weight: 4.5 parts of tortoise-plastron glue, 4.5 parts of turtle shell glue, 3 parts of antler glue; 6 parts of monkshood, 15 parts of negundo chastetree fruit, 9 parts of prepared rehmannia root, 6 parts of cocklebur fruit, 15 parts of raw astragalus root, 7.5 parts of fried codonopsis pilosula, 9 parts of epimedium herb, 6 parts of curculigo orchioides, 4.5 parts of spina gleditsiae, 15 parts of radix rehmanniae recen, 15 parts of mother-of-pearl, 15 parts of dandelion, 15 parts of oldenlandia diffusa, 7.5 parts of gypsum, 6 parts of baked ginger carbon and 4.5 parts of honey-fried licorice root.

3. The traditional Chinese medicine composition according to any one of claims 1 to 2, wherein the traditional Chinese medicine composition is prepared into a clinically acceptable pharmaceutical preparation according to a conventional traditional Chinese medicine preparation method.

4. The traditional Chinese medicine composition of claim 3, wherein the pharmaceutical preparation is a granule, powder, capsule, tablet or oral liquid.

5. Use of the Chinese medicinal composition of any one of claims 1-2 in the preparation of a medicament for treating asthma.

6. The use according to claim 5, wherein said asthma is asthmatic with yang deficiency.

7. The use of claim 6, wherein the asthma is asthma-like asthma with yang-deficiency, rheumatic stasis.

8. A medicament for treating asthma, which is prepared from the Chinese medicinal composition as claimed in any one of claims 1 to 2 and pharmaceutically acceptable adjuvants.

9. The medicament of claim 8, wherein the preparation method comprises:

(1) decocting the raw materials in water for 1-2 hr;

(2) and (4) leaching out juice, precipitating, taking clear liquid, adding pharmaceutically acceptable auxiliary agents, and bottling for later use.