WO2022037561A1

WO2022037561A1 - Traditional chinese medicine composition for treating asthma and application thereof

Info

Publication number: WO2022037561A1
Application number: PCT/CN2021/112923
Authority: WO
Inventors: 鹿振辉; 张惠勇; 张彤; 马子风; 李翠; 薛玲娜
Original assignee: 上海中医药大学附属龙华医院
Priority date: 2020-08-20
Filing date: 2021-08-17
Publication date: 2022-02-24
Also published as: CN111870681B; CN111870681A

Abstract

The present invention relates to a Traditional Chinese medicine composition for treating asthma and an application thereof. The Traditional Chinese medicine composition consists of the following active pharmaceutical ingredients in parts by weight: 4.5 parts of glue of tortoise plastron, 4.5 parts of turtle shell glue, 3 parts of antler glue, 6 parts of aconitum carmichaeli debx., 15 parts of negundo chastetree fruit, 9 parts of prepared rehmannia glutinosa, 6 parts of cocklebur fruit, 15 parts of radix astragali root, 7.5 parts of fried codonopsis pilosula, 9 parts of herba epimedii, 6 parts of curculigo orchioides, 4.5 parts of chinese honeylocust spine, 15 parts of dried rehmannia root, 15 parts of nacre, 15 parts of dandelion, 15 parts of spreading hedyotis herb, 7.5 parts of gypsum, 6 parts of prepared zingiber offcinale rose, and 4.5 parts of radix glycyrrhizae preparate. The composition of the present invention has the functions of warming yang, facilitating the flow of the lung-qi, dispelling coldness, tonifying primoradial ying and primoradial yang, and consolidating vital base and supplementing primordial qi for the lung and kidney insufficiencies in asthma, and also can adjust the immune function of a human body, warm yang and replenish essence, and maintain healthy qi for removing unhealthy qi. The present invention has the following advantages: a treatment effect is definite, it is safe to use, and an experimental result indicates that no obvious anomaly is found by monitoring liver and renal functions, and an electrocardiogram.

Description

A kind of traditional Chinese medicine composition for treating asthma and its application

technical field

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

Background technique

Bronchial asthma (referred to as asthma) is a heterogeneous clinical syndrome characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing, characterized by airway inflammation, airflow obstruction, and airway hyperresponsiveness (AHR). As one of the common chronic respiratory diseases, it affects more than 300 million people in the world, and the number of asthma patients is increasing year by year. Asthma is chronic and differentiated, and cannot be cured. There are still many bottlenecks and difficulties in the current standardized treatment plan (GINA). In recent years, the Global Asthma Prevention and Control Initiative has emphasized that the goal of asthma treatment is to achieve "overall control of asthma", both to achieve current control and to reduce future risks. It is recommended that patients with asthma adopt a long-term step-by-step treatment plan. Among them, Western medicine inhaled glucocorticoids and Long-acting beta-adrenergic agonists are the treatment of choice for most asthma patients. Although most patients can benefit from these treatments, the long-term use of the above-mentioned drugs may cause side effects such as adrenal suppression, allergic reactions and osteoporosis, which will greatly reduce the treatment compliance of some patients, and the disease cannot be effectively controlled. Even resulting in aggravation of the disease, the quality of life of many patients has not been improved as it should, so it is necessary to find new treatment plans and measures. Asthma has multiple clinical phenotypes due to differences in the dominant direction of airway immune inflammatory responses, and the treatment regimens have large group/individual differences, requiring multi-target intervention.

Theoretical basis for traditional medicine in the prior art:

Asthma belongs to the categories of "asthma syndrome", "asthma syndrome", "phlegm-drinking" and "shangqi" in traditional Chinese medicine. Traditional Chinese medicine has a long history of treating asthma and has accumulated rich clinical experience. "Warm Yang Method" is one of the main basic principles of bronchial asthma treatment. As early as in the Han Dynasty, Zhang Zhongjing advocated in "Treatise on Febrile Diseases and Miscellaneous Diseases" that "those who drink phlegm should be treated with mild medicine".

Traditional Chinese medicine's understanding of the pathological mechanism of patients with symptoms (chronic persistent period, attack period) is mostly concentrated in: deficiency (yang deficiency, qi deficiency), cold (deficiency cold, cold evil), wind (external wind, internal wind), phlegm There are five main pathological links including stasis and blood stasis, and there are mutual pathogenic factors between each link. TCM syndrome differentiation is mostly divided into four main syndrome types: cold wheezing syndrome, hot wheezing syndrome, wind wheezing syndrome, and deficiency wheezing syndrome. , Asthma syndrome is more in line with the characteristics of chronic persistent disease. Advantages of traditional Chinese medicine in the treatment of chronic persistent (refractory) bronchial asthma: The traditional Chinese medicine compound intervention starts from the whole of the sick person, and uses medicine from the perspective of the overall disease. It has multiple targets, a wide range of effects, and is not resistant to drug resistance. At the same time, the flexibility of the drug formulation makes its means more abundant; many studies have shown that long-term application of traditional Chinese medicine treatment can gradually reduce the amount of hormones (inhalation/oral) used, and some patients can completely withdraw hormones. It is easy to stabilize; Chinese medicine has a relatively wide range of immune regulation effects (commonly known as Chinese medicine can supplement deficiency, etc.), and can regulate the imbalance of the immune system of asthma patients through methods such as strengthening the body and expelling evil spirits, improving the patient's cellular immunity and airway defense. Asthma recurring or chronic persistently significantly reduced due to upper airway infection; many drugs in traditional Chinese medicine have direct antispasmodic, antiasthmatic, phlegm-relieving and anti-inflammatory effects, which can directly improve the clinical symptoms and airway inflammatory state of patients, and make asthma more severe. It is easy to achieve the control target, and the control stability is improved.

A summary of ancient literature:

As early as the "Neijing" era of traditional Chinese medicine, although there is no such thing as asthma, but there are records of its symptoms and characteristics, "Plain Questions": "Thus, those who commit thieves and wind-deficiency pathogens, if the yang receives it, will enter the six fu organs. If the yin receives it, Then it enters the five viscera. When it enters the six viscera, the body becomes hot, lying down from time to time, and the upper part is wheezing." "The cold air is in the Chong pulse and the panting is easy to handle." "Because of the heat, sweat, and panting and drinking." "Husband Those who cannot lie down and suffer from asthma are the guests of water and qi." "Therefore, the lower part of the water disease is swollen elbows and the abdomen, and the upper part is wheezing and breathing. Those who cannot lie down are all diseased. Therefore, the lungs are wheezing and the kidneys are edema. "Those who suffer from asthma and cough are water qi and yangming." "When the disease falls like a throbbing, because the blood is under the flank, it makes people gasp." If it doesn’t work, the heart will bulge, and the air will be violent and wheezing.” “The evil guest in the hand-Yangming network will make people full of qi in the chest, wheezing and bronchial amines.” “Those who cannot lie down but have a sound when breathing is the opposite of Yangming. Also." "Yangming Jue Ni, cough and body heat, good for epistaxis, hematemesis." "If the lung is small, you drink less, but if you are not sick, you drink more; if the lung is large, you drink more, and it is good for the chest and throat. Then the upper qi will stop coughing at the shoulders; if the lung is lower, the lung will be forced by the lung, which is good for the pain under the flank. If the lung is firm, the upper qi will not be coughed; Migraine chest pain." "Pulmonary disease, wheezing and coughing against the air, shoulder and back pain, sweating." "The lung is congested, and the panting will be full in two months." "The evil in the lung will cause skin pain, cold and heat on top of asthma, sweating. Coughing and moving the shoulders and back." "All kinds of dyspnea, asthma and vomiting belong to the superior." "As a result of night walking, dyspnea arises from the kidneys, and lustful qi infects the lungs; there is fear of falling, wheezing from the liver, and lustful qi harms the spleen; there are The panic comes from the lungs, the lustful qi is sad; the water falls and the breath comes from the kidneys and bones." "If the husband lives and breathes with sound, the collaterals of the lungs are reversed." "The five viscera and six organs are all disturbing. Cough, it's not just the lung." "It's all about the stomach, and it's about the lung."

"Yi Guan" says: "The real essence is depleted, and the panting comes out of the kidney qi and rushes...the qi does not return to the Yuan." If the patient's kidney yang is deficient, the lower element is not solid, the kidney does not control water, the water evil overflows, the heart invades the lung, the lung qi goes up, and asthma occurs. White, thin or slow pulse. Traditional Chinese medicine believes that the occurrence and progression of asthma syndrome (bronchial asthma) is closely related to "cold" (including deficient cold and real cold).

Zhang Zhongjing of the Han Dynasty pointed out that Fuyin, phlegm and turbidity are related to the pathogenesis of asthma: "Treatise on Febrile Diseases" "Chanjia Zuo, Guizhi Decoction and Houpu Xingzijia; ” and “Treatment of Pulse Syndrome and Syndrome of Phlegm and Drinking Diseases”, there are “coughing and rising qi, and the sound of water and chicken in the throat”, “the person is wheezing, the eyes are like falling off”, “the cough is against the upper qi, and the saliva is always cloudy, but it is impossible to sit. Sleeping". There is "sick phlegm on the diaphragm, full of asthma, cough and spit, cold and heat, back pain and back pain, and tears in the eyes, and people who are in a bright drama must have a drink." The proposed "sick phlegm drinker, It is a major criterion for clinical treatment of asthma.

Zhang Jingyue of the Ming Dynasty pointed out: "Asthma has perennial roots, and it occurs when it encounters cold, or when it is overworked, and it is also called asthma." "The Cause of Asthma," "The Cause of Asthma, the retention of phlegm and drink... or external When the wind and cold are brought to bear on the surface of the muscles, the symptoms of asthma will begin.”

In the Qing Dynasty, Lin Peiqin discussed in "Similar Syndrome Treatment Diagnosis and Treatment of Asthma Syndrome" that "if two days are insufficient, the spleen and kidneys are deficient, taming the wind and subduing the lung meridian, and frequent asthma attacks; congenital deficiency, too much sour and sweet, attacked by wind and cold. The phlegm-drinking illusion is like glue and lacquer, forming a nest and a mortar, sticking in the lung system, and fighting with the qi in and out of the breath."

Warming yang method of traditional Chinese medicine is the main treatment method for bronchial asthma, and the traditional Chinese medicine compound has obvious multi-target effect characteristics. Consumer interest in TCM as a complementary and alternative treatment in Western countries has grown dramatically over the past decade. According to the theory of traditional Chinese medicine, qi deficiency is one of the reasons for persistent asthma attacks. If qi deficiency is accompanied by wind-phlegm stasis syndrome, the symptoms of asthma patients are difficult to control, and Yanghe Dingchuan ointment is aimed at this pathogenesis. Based on the theory of traditional Chinese medicine disease prevention and treatment, the traditional Chinese medicine compound prescriptions with verified clinical efficacy can help supplement the treatment plan of asthma and bring new drug choices to patients.

After research, Yanghe Dingchuan cream has the functions of warming the yang, dispelling the lung and dispelling cold, replenishing the yin and yang, and cultivating the essence of the lung and kidney deficiency of asthma. Its efficacy is not only reflected in strengthening Yang and cultivating qi, dispelling cold and condensing phlegm, calming asthma and relieving qi; it can also regulate human immune function, warm yang and fill essence, and support righteousness to help dispel pathogens.

The clinical advantages of Yanghe Dingchuan ointment of the present invention compared with similar varieties already on the market:

Yanghe Dingchuan ointment is not only effective, but also safe to use. Through the monitoring of the three major routines, liver and kidney function and electrocardiogram, no obvious abnormality was found, and there was no toxic side effect in clinical application.

Variety Feasibility Analysis:

Tracheal asthma (referred to as asthma) is a heterogeneous clinical syndrome, one of the most common chronic respiratory diseases, affecting more than 300 million people worldwide, and the number of asthma patients is increasing year by year. WHO predicts that there will be 100 million new cases of asthma by 2025, and asthma will bring a heavy burden to governments, families and patients in various countries. Since GINA proposed the concept of "asthma control" in 2006, in 2019, it emphasized the treatment goal of "overall control" while reducing future risks such as acute exacerbations and death. However, the asthma control rates in Europe, Asia-Pacific countries, and my country are far from reaching the GINA target, and some patients have greater psychological resistance and poor compliance with GINA long-term treatment. In recent years, more and more studies have shown that the addition of traditional Chinese medicine can reduce the dose of control drugs (inhaled hormones), and even eliminate the need for long-term inhaled hormone therapy.

Guidelines for Clinical Application of Chinese Patent Medicines-Respiratory System Diseases (2016 Edition) The available Chinese patent medicines include Haizhu Chuanxiding Tablets, Suhuang Zhike Capsules and Zhichuanling Oral Oral Liquid, soothes wind and disperses the lung, relieves acuteness and relieves spasm, lowers qi and relieves asthma; but the ingredients contained in Haizhu Chuanxi Ding tablets will cause a greater burden on the spleen and stomach and cannot be taken for a long time. The main effect of Suhuang Zhike Capsule is to treat dry and itchy throat. , repeated dry cough without phlegm, relieving cough and sore throat, etc., the therapeutic effect on relieving asthma is not very obvious; for asthma syndrome (low voice and short breath, breathing is worse when moving, fatigue and pulse deficiency), Chinese patent medicine Suzi Jiangqi Pill, Gecko can be used. Dingchuan capsule and Chuankezhi injection. Gecko Dingchuan Capsule has the effect of nourishing yin and clearing lung, relieving cough and relieving asthma; For qi inversion and phlegm congestion, cough and wheezing, thoracic and diaphragmatic congestion. Suzi Jiangqi Pill is mainly used to treat consumptive cough, asthma, shortness of breath, chest fullness, spontaneous sweating and night sweats caused by deficiency of both lungs and kidneys, deficiency of yin and heat in the lungs, and those with deficiency of yin and red tongue without coating should not be taken. Due to its warm and dry nature, it is not suitable for asthma and cough due to deficiency of both lung and kidney, lung heat and phlegm.

Yanghe Dingchuan ointment is used for asthma patients with yang deficiency type. Yanghe compound formula is composed of filling essence, warming yang, dispelling cold and clearing stagnation. Machines coincide. Deer horn glue nourishes blood and essence, nourishes kidney and helps yang, turtle shell glue nourishes yin and yang, nourishes kidney and strengthens bones, turtle shell glue nourishes yin and nourishes blood, rehmannia glutinosa nourishes yin and blood, fills essence and marrow, aconite expels cold and dehumidifies, nourishes fire and helps yang, Huang Jingzi Dispelling wind, relieving external appearance, relieving cough and relieving asthma, the combined use of monarch medicine has the effects of warming yang and dispersing lung, strengthening the root and cultivating vitality, and absorbing Qi and calming asthma; All are ministerial medicines. Codonopsis pilosula invigorates qi and strengthens the spleen. Astragalus nourishes qi and strengthens the surface to help Codonopsis pilosula. The celestial root and celestial spirit spleen tonify kidney yang, warm spleen yang, and strengthen muscles and bones. The medicine has spleen-yang, kidney-yang, and Wei-yang triple burners to treat together, and strongly helps the monarch medicine to consolidate Yang and nourish phlegm, dispel cold and condense phlegm, and promote the recovery of Yuan-yang deficiency with the heat of triple burner Yang; Rehmannia glutinosa, mother of pearl, dandelion , Hedyotis diffusa and gypsum are adjuvants, clearing heat, promoting body fluid and nourishing yin, mother of pearl liver subduing yang, clearing liver and improving eyesight, tranquilizing the mind and soothing the mind, dandelion, Hedyotis diffusa and gypsum clearing heat and detoxifying, adjuvants on the one hand counteract and help. Yang medicines are easy to cause heart and liver deficiency and fire to generate endogenously, and although phlegm is heated by medicines, it can resolve phlegm-heat. Use to help yang consolidate the root without leaving evil; fire ginger charcoal and licorice are used as medicines, reconcile various medicines, neutralize phlegm and dampness, and also astringe and solidify lung qi. The above compatibility has the effects of warming the yang and dispersing the lung, strengthening the body and nourishing the vitality, and absorbing the qi and calming the asthma. Starting from the fundamental pathogenesis of bronchial asthma, "Yang deficiency and cold phlegm in the phlegm", it can treat both the symptoms and the symptoms, and overcome the deficiencies of the above-mentioned Chinese patent medicines in the treatment of asthma. Regulates the imbalanced state of the immune system in patients with asthma, improves the cellular immunity and airway defense functions of patients, and makes patients with upper airway infection-induced recurrent asthma attacks or a significant reduction in chronic chronicity; it has direct antispasmodic, relieving asthma, and anti-inflammatory effects. It can directly improve the clinical symptoms and airway inflammation state of patients, making it easier for asthma to achieve the goal of control, and the control stability is improved.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a traditional Chinese medicine composition for the effective treatment of asthma, aiming at the deficiencies of the prior art.

For realizing the above-mentioned purpose, the technical scheme that the present invention takes is:

First, the present invention provides a traditional Chinese medicine composition for treating asthma, the traditional Chinese medicine composition is composed of the following raw materials by weight: 4-5 parts of turtle glue, 4-5 parts of turtle glue, 2-4 parts of antler glue servings, Fuzi 5-7 servings, Huang Jingzi 14-16 servings, Rehmannia glutinosa 8-10 servings, Xanthium 5-7 servings, Raw Astragalus 14-16 servings, Fried Codonopsis 7-8 servings, Xianlingpi 8-10 servings , Curcuma 5-7 parts, Saponin 4-6 parts, Rehmannia 14-16 parts, Mother of Pearl 14-16 parts, Dandelion 14-16 parts, Hedyotis diffusa 14-16 parts, Gypsum 7-8 parts , 5-7 parts of ginger charcoal, 4-5 parts of licorice.

Preferably, the traditional Chinese medicine composition is composed of the following raw materials by weight: 4.5 parts of tortoise shell glue, 4.5 parts of turtle shell glue, 3 parts of antler glue; 6 parts of seed, 15 parts of raw Astragalus, 7.5 parts of fried Codonopsis, 9 parts of Xianlingpi, 6 parts of Curcuma, 4.5 parts of Saponin, 15 parts of Rehmannia glutinosa, 15 parts of mother of pearl, 15 parts of dandelion, 15 parts of Hedyotis diffusa parts, 7.5 parts of gypsum, 6 parts of ginger charcoal, 4.5 parts of licorice.

More preferably, the traditional Chinese medicine composition is prepared into a clinically acceptable pharmaceutical preparation according to the conventional preparation method of traditional Chinese medicine, and the pharmaceutical preparation is a granule, a powder, a capsule, a tablet or an oral liquid.

Secondly, the present invention also provides the application of the above-mentioned traditional Chinese medicine composition in preparing a medicine for treating asthma.

Preferably, the asthma is Yang deficiency type asthma.

More preferably, the asthma is a type of asthma with Yang deficiency, rheumatism and blood stasis syndrome.

Yanghe Dingchuan Ointment is an externally processed preparation entrusted by our hospital. After observing the efficacy and safety of more than 100 patients with bronchial asthma, the patients responded well, and there were no toxic and side effects, and no similar products were available in the market. The main function of this recipe is to warm the yang, disperse the lung and disperse cold, cultivate the essence, strengthen the root, and relieve the asthma. In the prescription, antler glue, turtle shell glue, turtle shell glue, rehmannia glutinosa, aconite, and Vitex japonica are the king medicines. Deer antler glue nourishes blood and essence, nourishes kidney and helps yang, tortoise shell glue nourishes yin and yang, nourishes kidney and strengthens bones, and turtle shell glue nourishes Yin and blood, Rehmannia glutinosa to nourish yin and blood, fill essence and nourish marrow, Aconite to dispel cold and dehumidify, invigorate fire and help yang, Huang Jingzi expel wind and relieve external appearance, relieve cough and relieve asthma. Peiyuan solidifies the root of lung and kidney deficiency in asthma; raw Astragalus, fried Codonopsis, Curcuma, Xianlingpi, Xanthium, and Saponin are all used as ministerial medicines, Codonopsis spleen, invigorates spleen, and astragalus nourishes qi and solidifies the table to help Codonopsis righting The power of Xian Mao and Xian Ling spleen tonifies kidney yang, warms spleen yang, and strengthens muscles and bones. Xanthium has the effects of dispersing wind and removing dampness, clearing orifices and relieving pain. Cultivating Yuan, dispelling cold and condensing phlegm, promoting the recovery of Yuan Yang deficiency with the qi of Sanjiao Yang heat; Rehmannia glutinosa, mother of pearl, dandelion, Hedyotis diffusa, gypsum as adjuvants, clearing heat, producing body fluid and nourishing yin, mother of pearl Liver subdues yang, clears liver and improves eyesight, calms the mind and calms the mind. Dandelion, Hedyotis diffusa and gypsum clear heat and detoxify. On the one hand, the adjuvant counteracts the disadvantages of yang-boosting drugs, which are easy to cause heart and liver deficiency and fire to be endogenous. On the other hand, the exogenous pathogens invading the lungs are easy to turn into heat and toxins due to poor control of asthma, and the opposite is the combination of cold and heat, deficiency and excess, and the five internal organs are taken into account, so as to help yang consolidate the root without leaving the evil; , Reconcile various medicines, and neutralize phlegm-dampness, and also astringe and solidify lung-qi. The above compatibility can not only warm yang, disperse cold and resolve phlegm, but also coordinate the exterior and interior, clear qi and detoxify, and take into account qi and yin. Combination of various medicines can work together to warm yang, resist cold and expel phlegm.

Source of prescription:

Zhang Zhongjing's "Treatise on Febrile Diseases" in the Han Dynasty proposed that "those who are sick with phlegm should be treated with warm medicine", which is a major criterion for clinical treatment of asthma. Wang Hongxu of the Qing Dynasty stated that "Yanghe Decoction" has the effect of warming Yang and nourishing blood, dispelling cold and stagnation, and proposed the principle of "Yanghe". Based on its ability of warming yang, dispelling cold and dispelling stagnation, and the thinking of "same treatment for different diseases" in traditional Chinese medicine, combined with TCM syndrome differentiation, it has been widely used in the treatment of various diseases with yang deficiency and cold coagulation syndrome. The addition and subtraction of the cut forms Yanghe Dingchuan cream.

Source department:

Longhua Hospital Pulmonary Disease Research Team/Respiratory Disease Research Institute

Clinical features of the department:

The combination of traditional Chinese and Western medicine prevents and treats respiratory diseases, and highlights the important department characteristics of applying "warm yang and anti-cold method" to treat airway diseases (bronchial asthma, COPD, bronchiectasis, etc.) according to the theory of traditional Chinese medicine.

Source details:

The idea of formulating this prescription is mainly derived from the classic Yanghe decoction formula and its viewpoints published by Wang Hongxu of the Qing Dynasty in 1740, and the earliest proposal of the “Warm Yang Anti-cold Method” in the 1990s. Based on the academic viewpoints on the treatment of bronchial asthma, the pulmonary disease team has carried out related clinical practice, standardized clinical research, and basic research work around the traditional Chinese medicine Wenyang treatment for a long time. Focusing on the application of "The Method of Yang Harmony" in the prevention and treatment of chronic persistent bronchial asthma (refractory asthma) and the optimization of effective compounds ”, carried out long-term clinical practice optimization research, established multi-dimensional animal models and experimental platforms for basic research on bronchial asthma and international benchmarks, and further based on lung/airway immune verification, respiratory dynamics and its molecular mechanism related series In-depth research work. Afterwards, according to the international standards, the multi-center RCT trial for the treatment of chronic persistent (refractory) bronchial asthma was carried out to carry out evidence-based evaluation research work. The group assessed that it could clearly solve the clinical problems, and the formulation optimization was completed, and finally Yanghe Dingchuan ointment was formed.

Main functions:

It has the effects of warming the yang and dispersing the lung, strengthening the body and cultivating the essence, and absorbing the qi to relieve asthma. It is used for asthma patients with yang deficiency type.

The theory of traditional Chinese medicine to adapt to the etiology of the disease:

Asthma belongs to the categories of "asthma syndrome", "asthma syndrome", "phlegm-drinking" and "shangqi" in traditional Chinese medicine. Traditional Chinese medicine's understanding of the pathological mechanism of patients with symptoms (chronic persistent period, attack period) is mostly concentrated in: deficiency (yang deficiency, qi deficiency), cold (deficiency cold, cold evil), wind (external wind, internal wind), phlegm There are five main pathological links including stasis and blood stasis, and there are mutual pathogenic factors between each link. TCM Syndrome Differentiation.

The classification is mostly divided into four main syndrome types: cold wheezing syndrome, hot wheezing syndrome, wind wheezing syndrome, and deficiency wheezing syndrome. Asthma syndrome is more in line with the characteristics of chronic persistent disease.

Pathogenesis theory of traditional Chinese medicine

"Yang-deficiency and cold-phlegm accumulation" is the fundamental pathogenesis of bronchial asthma, "warming yang to fight cold and expel phlegm" is the main principle for the treatment of acute/chronic bronchial asthma, and "Yanghe Dingchuan ointment" is formulated with Wenyang Xuanfei Powder Cold, replenishing yin and yang, cultivating and strengthening this formula contain the essence of warming yang and resisting cold, which coincides with the pathogenesis of asthma, especially in patients with asthmatic deficiency.

Theory of Traditional Chinese Medicine

Yanghe Dingchuan ointment has the functions of warming yang, dispelling the lung and dispelling cold, replenishing yin and yang, and cultivating the essence of asthma. The spleen yang, kidney yang, and Wei yang three energizers are treated in the same way. The minister medicine strongly helps the monarch medicine to consolidate the yang and nourish the phlegm, dispel cold and condense the phlegm. On the one hand, the anti-yang drugs are easy to cause the heart and liver to be deficient and the fire is endogenous, and although the phlegm is hot, the phlegm heat is eliminated. Taking into account the deficiency and the real, the five internal organs, helps the yang to consolidate the root without leaving the evil.

Other theoretical basis: the current status of pharmacological research on various medicinal flavors in prescriptions

Medicated antler gum

Research status Deer horn gum has the functions of anti-inflammatory, analgesic and blood-activating, anti-mammary gland hyperplasia, gastric mucosal protection, anti-osteoporosis, blood-activating and aphrodisiac ^[1-5] .

Flavor: Turtle glue

Research status: It is mainly used for nourishing yin and nourishing blood, hemostasis and blood, nourishing kidney and strengthening bones, etc. It can promote cell proliferation, promote chondrocyte proliferation and inhibit cell apoptosis by regulating gene expression ^[6-7] .

Flavor: Turtle Gum

Research status: Turtle armor has definite and reliable curative effects in improving immunity and resisting liver fibrosis and pulmonary fibrosis, but this is different from the traditional Chinese medicine's use of turtle armor for the treatment of fever due to yin deficiency, fatigue due to heat, Gu steaming, and deficiency of wind. Movement, amenorrhea, and other diseases ^[8] .

Medicinal flavor Rehmannia glutinosa

Research status Rehmannia glutinosa pharmacological function and activity in the blood system, immune system, endocrine system, cardiovascular system and nervous system, as well as anti-tumor, anti-aging and other aspects of the role ^[9] .

Medicinal aconite

Research status The main components of aconite are alkaloids, among which C-19 type diterpene alkaloids with aconitine skeleton are the main components, followed by C-20 type diterpene alkaloids, and the most common types are heptidine and vertepine. The main skeleton types are alkaloids, naproline, and delphine; in addition to alkaloids, it also contains flavonoids, saponins, ceramides and other ingredients. The biological activities of aconite mainly include cardiotonic, anti-tumor, anti-inflammatory and analgesic, immune-enhancing, and anti-aging effects ^[10] .

Medicinal Flavor

Research status It has immune enhancement, antipyretic and analgesic, antibacterial, anticancer and anti-inflammatory ^[11] .

Medicinal Flavor Astragalus

Research status Astragalus polysaccharide can effectively increase the activity of macrophages, improve the function of T cells and B cells, enhance the immunity of the body, and promote the recovery of the disease; it can also regulate the immune function of asthma patients; it can protect the liver and strengthen the immunity. , lowering blood pressure, hypoglycemic and lipid-lowering, antibacterial and antitumor effects ^[12] .

Medicinal Codonopsis

Research status Codonopsis radix extract has obvious inhibitory effect on Escherichia coli, Staphylococcus aureus, Streptococcus and Salmonella in vitro, and has the functions of enhancing immunity, anti-oxidation, anti-fatigue, protecting nerves, antibacterial and anti-inflammatory ^[13] .

Medicinal flavor fairy spirit spleen

Research status Icariin is one of the main active components of Epimedium, with immunomodulatory, anti-inflammatory, anti-aging, anti-tumor and other activities, and can improve osteoporosis, Alzheimer's disease, Parkinson's disease, cerebral ischemia, etc. , atherosclerosis, rheumatism and other symptoms of diseases. Its pharmacological activities include: promoting the generation and activation of osteoblasts, inhibiting the formation and function of osteoclasts, alleviating osteoporosis; inhibiting the production of β-amyloid, hyperphosphorylation of tau protein and the reduction of dopamine content to protect nerves system; protect the cardiovascular system by protecting cardiomyocytes, increase the number of cardiomyocytes, and improve endothelial dysfunction; promote the function of reproductive organs; regulate the immune system by regulating T cell balance ^[14] .

Medicinal Curcuma

Research status Curcuma currant has the functions of dissipating carbuncle, strengthening muscles and bones, expelling cold and dampness, invigorating kidney yang, nourishing essence and blood, etc. Modern pharmacological research shows that Curcuma curcuma has antioxidant, immune regulation, anti-osteoporosis, kidney and yang, liver protection, nerve protection and other activities ^[15] .

Medicinal smell Xanthium

Research status As a traditional Chinese medicine, Xanthium mainly contains volatile oils, fatty acids, phenolic acids, lignans, sesquiterpene lactones, thiazide-dione heterocycles and other chemical components, which have anti-inflammatory and analgesic properties. , antibacterial, antiviral, hypoglycemic, hypolipidemic, antitumor and other pharmacological effects ^[16] .

Medicinal Flavor

Current research status Saponin thorn is a traditional Chinese medicine, which has the functions of sterilizing and penetrating pus, searching for wind, killing insects, etc. Modern research has found that saponin thorn is mainly composed of triterpenes and saponins, flavonoids, phenolic acids, echinoic acid glycosides, coumarin and other chemicals It has the functions of antibacterial, antiviral, improving immunity, anti-oxidation, anti-tumor, anti-coagulation, inhibiting thrombosis, inhibiting the proliferation of venous endothelial cells, and also has an effect on cardiovascular and cerebrovascular ^[17] .

medicinal flavor

Research status Rehmannia polysaccharide can enhance the body's immune function[18], mainly in promoting the growth of immune organs and normal lymphocyte proliferation and differentiation, enhancing the phagocytic function of macrophages, and stimulating the production and release of cytokines.

Medicinal Dandelion

Research status It has antibacterial, anti-inflammatory, antioxidant, and gastrointestinal tract protection effects ^[18] . Dandelion has a broad-spectrum antibacterial effect, and has different degrees of inhibition on various pathogenic microorganisms such as Gram-positive bacteria, Gram-negative bacteria, fungi, and spirochetes. Dandelion has good effect and safety in the treatment of acute mastitis, ulcerative colitis and acute suppurative tonsillitis during lactation.

Medicated Mother of Pearl

Research status The pharmacological effects of mother-of-pearl mainly include sedative, antioxidant, anti-acute liver injury, neutralizing gastric acid, and regulating immunity ^[19] .

Medicinal Flavor Hedyotis diffusa

Research status Hedyotis diffusa is an annual hairless slender scattered herb, which can inhibit pneumococcus, staphylococcus aureus and dysentery bacillus and other bacteria, and has the effect of enhancing immunity. It is a rare "good medicine" ^[20] .

medicinal gypsum

Research status It has the functions of antipyretic, immune regulation and antiviral ^[6] . Gypsum can inhibit the excessively excited body temperature center during fever, and has a strong and rapid antipyretic effect; it can adjust the balance of T lymphocytes; increase the phagocytic ability of rabbit alveolar macrophages to Staphylococcus leukemia and colloidal gold; The body is free from viruses.

Licorice

Research status It has pharmacological effects such as antibacterial, antioxidant, anti-inflammatory, immune regulation, anti-ulcer, detoxification, anti-cancer, and anti-liver fibrosis ^[20] .

Use of prescriptions in this medical institution

This product has been used in this medical institution for 7 years (October 2013 to August 2020)

Description of the specific situation

The idea of formulating this prescription is mainly derived from the classic Yanghe decoction and its viewpoints in the "Complete Collection of Surgery" published by Wang Hongxu of the Qing Dynasty in 1740, as well as the idea of "Wen Yang Kang" proposed by Professor Wu Yingen, a senior of the discipline team in the 1990s. The research and development team has carried out a series of clinical and basic researches on the treatment of bronchial asthma with the "Warm Yang Anti-cold Method" for more than 20 years, and formed the in-hospital preparation "Wen Yang Anti-Cold Mixture" in our hospital, thus establishing the Based on the treatment principles of warming yang, resisting cold and eliminating phlegm, the compound formula of Yang and Dingchuan was preliminarily formulated. Warm Yang Anti-cold Mixture (10g each of Aconite, Scutellaria baicalensis, Peach Kernel, Baked Ephedra, 5g Asarum, 3g Saxifrage, 2 Centipedes, 3g Whole Scorpion) is flavored on the basis of Mahuang Fuzi Xixin Decoction, (1 ) mainly treats the acute exacerbation period of asthma, and the TCM dialectical is cold asthma. (2) There is no GINA guideline for the prevention and treatment of asthma in the research and development stage, and the problems faced are different from the current stage. The Wenyang Anticold Mixture is aconite, skullcap, peach kernel, ephedra, asarum, saxifrage, centipede and whole scorpion, and only one flavor of aconite is the same as Yanghe Dingchuan ointment; "Professor Wu Yingen's clinical experience in treating bronchial asthma Summary "The treatment of asthma is mainly based on the Kechuan Liuwei Mixture (Fuzi, Scutellaria baicalensis, Peach Kernel, Zhi Ma Huang, Asarum, Saxifuga) and Zhichuan Capsules (Xianlingpi, Morinda and Helicobacter) based on Zhongjing Mahuang Fuzi Xixin Decoction. Cnidium) and Morinda officinalis of Chuan Capsules treat patients with simple kidney-yang deficiency in stable stage; Yanghe Dingchuan ointment is based on Qing Wang Hongxu's "Yang and" viewpoint and the lung disease research team's many years of clinical experience, using "Yin-Yang treatment, Qi "Xueshuangbu" method in the treatment of chronic persistent deficiency asthma——According to the Chinese Medical Association Respiratory Disease Branch Asthma Group. Bronchial Asthma Prevention and Treatment Guidelines (2016 Edition) Bronchial Asthma Differentiation and Treatment, Combined with ICS in the Treatment of Global Bronchial Asthma Prevention and Treatment Proposal ( Incompletely controlled asthma patients with GINA)→Reduce ICS dosage and reduce side effects→Discontinue. The related content is not disclosed in the prior art of the party of this patent. In the seven years from October 2013 to August 2020, the lung disease research team of our hospital has undertaken a number of projects for the prevention and treatment of airway diseases with traditional Chinese medicine. The clinical research and basic research of compound prescription for treating deficiency-cold cough and asthma, chronic persistent deficiency asthma, and obesity asthma have accumulated a certain sample size of clinical data and basic research data, which has laid the foundation for the clinical application and promotion of Yanghe Dingchuan Ointment. Details are as follows.

In October 2013, the team undertook the project of the Shanghai Municipal Science and Technology Commission (13401905400)--the research on the optimization of the characteristic diagnosis and treatment plan of "winter disease and summer treatment" for deficiency-cold cough and asthma. A small-sample clinical observational study on the treatment of bronchial asthma with Yanghe compound formula was initially carried out, and more than 100 cases were included.

In October 2016, the team began to be responsible for promoting the research on the immune regulation mechanism of Yanghe decoction in patients with chronic persistent asthma (LYTD-36(D36)). A small sample clinical observational study of Chuan Compound in the treatment of bronchial asthma, including more than 90 cases of bronchial asthma, and collecting peripheral blood and induced sputum samples of patients before and after treatment to study the relationship between the cellular immunity and the changes of airway microbial colonies. "Addition and subtraction have provided research ideas and solutions on the regulation and effect mechanism of airway microorganisms in patients with chronic persistent asthma and the possible immune mechanism of patients with chronic persistent asthma, and broadened the clinical treatment and research ideas for refractory asthma. It has good research value.

In November 2017, the team was responsible for promoting the Haishenkang Hospital Development Center Project (SHDC12017118) - a research project on the diagnosis of bronchial asthma (chronic persistent) with integrated traditional Chinese and Western medicine. The joint hospital and Zhongshan Hospital Affiliated to Fudan University, etc.) carried out a multi-center clinical study on the treatment of bronchial asthma with Yanghe Dingchuan Compound and the clinical observation of the agreed prescription (September 2017-September 2020). More than 80 cases of Yanghe Dingchuan have been completed. Clinical observation of Dingchuan recipe in the treatment of bronchial asthma. Preliminary research results show that Yanghe Dingchuan compound has definite curative effect and high safety in the treatment of bronchial asthma.

In September 2019, based on the previous research foundation, the team undertook the capacity building of the Longhua Hospital TCM Evidence-Based Medicine Research Center, a project of the State Administration of Traditional Chinese Medicine. As a starting point, under the guidance of TCM theory, build and improve evidence-based TCM clinical research design, evaluation technical specifications and quality assurance system. The randomized controlled clinical trial project started with chronic persistent asthma that is difficult to control in the clinic. The combination of traditional Chinese and Western medicine was used to carry out RCT clinical research to further clarify the efficacy characteristics and safety of traditional Chinese medicine in improving the control rate of chronic persistent asthma. , to provide high-quality evidence-based support for asthma prevention and treatment of traditional Chinese medicine programs/compounds; at the same time, exploratory research on the regulation characteristics of traditional Chinese medicine on patients' overall cellular immunity and local airway microbial environment provides more theoretical basis for traditional Chinese medicine treatment of chronic persistent asthma. clinical thinking. And take this to further promote the clinical research capacity building of the Longhua Hospital Clinical Research Center, cultivate a team of professionals with evidence-based medicine thinking and ability, and have a high level of high-level clinical experiment design and organization. A technologically advanced technology platform for evidence-based research and evaluation of traditional Chinese medicine.

The advantages of the present invention are:

Aiming at the etiology and pathology of asthma with yang deficiency, rheumatism and blood stasis syndrome, the raw materials and the ratio between them are optimized, and the curative effect is remarkable and has no toxic and side effects. For some intractable asthma patients, its curative effect is remarkable. The synergistic effect of the various medicinal flavors in the prescription is in line with the compatibility of the "monarch, ministers and ministers". It not only has the functions of warming the yang, dispelling the lung and dispelling cold, replenishing the yin and yang, cultivating the root of the lung and kidney insufficiency of asthma, but also regulating the immune function of the human body. Warming the yang and filling the essence, supporting the righteous qi to help dispel the evil, bring new drug choices for the patients, and have a good application prospect.

Description of drawings

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

Figure 2 shows the changes in airway resistance and lung compliance of mice in each group after challenge with gradient methacholine (Mean±SE, n=6), ^* P<0.05; AS VSAT, ^# P<0.05.

Figures 3-5 are diagrams of leukocytes and classification flow analysis in lung tissue of mice in each group.

Figure 6 shows the results of HE staining of mouse lung tissue in each group (200 μm).

Figure 7 shows that in January 2016, the team undertook the National Natural Science Foundation of China Project Youth Fund (81503508), officially started the mechanism study of bronchial asthma, and initially explored the mechanism of Yanghe Compound in the treatment of asthma. The study found that the lung tissue of asthmatic mice CalcamRNA, IL- 5. The level of IL-17 was higher than that of healthy mice, and the levels of Calca mRNA, IL-5 and IL-17 decreased significantly after Yanghe decoction treatment. (Calca mRNA mainly encodes CGRP)

Figure 8 shows that in January 2020, based on the National Youth Project undertaken in 2016, it further undertook the General Fund of the National Natural Science Foundation of China (81973817) to study the effect of Yanghefang on the regional immune network of asthmatic mice through the synergistic activation of PNECs/ILCs. The study found that in the OVA-induced allergic asthma mouse model, Yanghe Fang could significantly reduce the infiltration of inflammatory cells such as EOS, lymphocytes, and macrophages in the bronchoalveolar lavage fluid, and reduce the number of ILC2 cells in the lung tissue.

detailed description

The present invention will be further described below in conjunction with specific embodiments. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that those skilled in the art can make various changes or modifications to the present invention after reading the contents described in the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Embodiment 1 Chinese medicine composition (one)

According to the following proportions by weight, the raw materials are obtained:

4 parts turtle shell glue, 4 parts turtle shell glue, 2 parts deer horn glue, 5 parts aconite, 14 parts Huang Jingzi, 8 parts Rehmannia glutinosa, 5 parts Xanthium, 14 parts raw Astragalus, 7 parts fried Codonopsis pilosula, 8 parts Xianlingpi , 5 parts of Curcuma, 4 parts of Saponin thorn, 14 parts of Rehmannia glutinosa, 14 parts of Mother of Pearl, 14 parts of Dandelion, 14 parts of Hedyotis diffusa, 7 parts of Gypsum, 5 parts of Pao Ginger Charcoal, 4 parts of licorice.

Embodiment 2 Chinese medicine composition (two)

5 parts turtle shell glue, 5 parts turtle shell glue, 4 parts antler glue, 7 parts aconite, 16 parts Huang Jingzi, 10 parts Rehmannia glutinosa, 7 parts cocklebur, 16 parts raw Astragalus, 8 parts fried Codonopsis pilosula, 10 parts Xianlingpi , 7 parts of Curcuma, 6 parts of Saponin thorn, 16 parts of Rehmannia glutinosa, 16 parts of Mother of Pearl, 16 parts of Dandelion, 16 parts of Hedyotis diffusa, 8 parts of Gypsum, 7 parts of Pao Ginger Charcoal, 5 parts of Zhi Licorice.

Embodiment 3 Chinese medicine composition (three)

4 parts turtle shell glue, 5 parts turtle shell glue, 2 parts antler glue, 7 parts aconite, 14 parts Huang Jingzi, 10 parts Rehmannia glutinosa, 5 parts cocklebur, 16 parts raw astragalus, 7 parts fried Codonopsis pilosula, 10 parts Xianlingpi , 5 parts of Curcuma, 6 parts of Saponin, 14 parts of Rehmannia glutinosa, 16 parts of Mother of Pearl, 14 parts of Dandelion, 16 parts of Hedyotis diffusa, 7 parts of Gypsum, 7 parts of Pao Ginger Charcoal, 4 parts of Zhigancao.

Embodiment 4 Chinese medicine composition (four)

5 parts turtle shell glue, 4 parts turtle shell glue, 4 parts deer horn glue, 5 parts aconite, 16 parts Huang Jingzi, 8 parts Rehmannia glutinosa, 7 parts Xanthium, 14 parts raw Astragalus, 8 parts fried Codonopsis pilosula, 8 parts Xianlingpi , 7 parts of Curcuma, 4 parts of Saponin thorn, 16 parts of Rehmannia glutinosa, 14 parts of Mother of Pearl, 16 parts of Dandelion, 14 parts of Hedyotis diffusa, 8 parts of Gypsum, 5 parts of Pao Ginger Charcoal, 5 parts of Zhi Licorice.

Embodiment 5 Chinese medicine composition (five)

4.5 parts turtle shell glue, 4.5 parts turtle shell glue, 3 parts deer horn glue, 6 parts aconite, 15 parts Huang Jingzi, 9 parts Rehmannia glutinosa, 6 parts cocklebur, 15 parts raw astragalus, 7.5 parts fried Codonopsis pilosula, 9 parts Xianlingpi Parts, Curcuma 6 parts, Saponin 4.5 parts, Rehmannia glutinosa 15 parts, Mother of Pearl 15 parts, Dandelion 15 parts, Hedyotis diffusa 15 parts, Gypsum 7.5 parts, Pao Ginger Charcoal 6 parts, Zhi Licorice 4.5 parts.

Example 6 Ointment

The preparation method is as follows:

Respectively, take the crude drug according to the proportion by weight described in Examples 1-5, add water for decocting for 1-2 hours, filter, concentrate the filtrate, cool to room temperature, concentrate the supernatant, add water, stir, let stand, and take the The clear liquid can be concentrated into clear paste.

Example 7 Granules

The preparation method is as follows:

Respectively, take the crude drug according to the proportion by weight described in Examples 1-5, add water for decocting for 1-2 hours, filter, concentrate the filtrate, cool to room temperature, concentrate the supernatant, add water, stir, let stand, and take the The clear liquid is concentrated into clear paste, and then the conventional adjuvant of granules is added.

Example 8 Tablet/Capsule

The preparation method is as follows:

Respectively, take the crude drug according to the proportion by weight described in Examples 1-5, add water for decocting for 1-2 hours, filter, concentrate the filtrate, cool to room temperature, concentrate the supernatant, add water, stir, let stand, and take the The clear liquid is concentrated into clear paste, and then conventional adjuvants for tablets/capsules are added.

Example 9 Clinical trial

1. Materials and methods

1. Data sources

A clinical observational study of Yanghe Compound in the treatment of bronchial asthma carried out by Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September 2016 to September 2019 was collected.

2. Diagnostic criteria ^[21]

Clinical symptoms and signs of typical asthma: (1) recurrent wheezing, shortness of breath, with or without chest tightness or cough, frequent at night and in the morning, often associated with exposure to allergens, cold air, physical and chemical stimuli, and upper respiratory tract infections (2) During the attack, scattered or diffuse wheezing can be heard in both lungs, and the expiratory phase is prolonged; (3) The above symptoms and signs can be relieved by treatment or by themselves.

Objective examination of variable airflow limitation: (1) positive bronchodilator test (after inhalation of bronchodilator, FEV1 increased by >12%, and the absolute value of FEV1 increased by >200m1); (2) bronchial challenge test was positive; (3) exhalation Peak expiratory flow (PEF) average daily diurnal variability rate (for 7 consecutive days, the sum of daily PEF diurnal variability rate/7)>10%, or PEF weekly variability rate {(the highest PEF value within 2 weeks - the lowest PEF value)/[(the highest PEF value in 2 weeks + the lowest PEF value)*1/2]×100%}>20%.

In line with the above symptoms and signs, and with any one of the objective examinations of airflow limitation, and excluding wheezing, shortness of breath, chest tightness and cough caused by other diseases, the diagnosis of asthma can be made.

3. Inclusion criteria

①Age is 15 to 75 years old;

② Patients diagnosed with chronic persistent asthma;

③ The asthma symptoms are not controlled for more than 3 months each year;

④ After being informed, they voluntarily participated in this study and signed the informed consent.

4. Exclusion criteria

①Combined with obvious upper/lower respiratory tract infection (virus/bacteria) within 4 weeks;

②Within 4 weeks or long-term continuous/intermittent oral/intravenous glucocorticoid therapy;

③ Use antibacterial drugs within 4 weeks;

④ History of fatal asthma attack;

⑤ Suffering from definite diagnosis of emphysema, tuberculosis, sarcoidosis, pulmonary fibrosis, lung cancer, etc.;

⑥Have suffered from serious heart disease, including: (1) angina pectoris; (2) myocardial infarction; (3) heart failure; (4) any other heart disease judged by the investigator to be inappropriate to participate in this trial;

⑦ Abnormal liver and kidney function or history of serious primary disease of liver and kidney;

⑧ History of serious primary diseases of hematopoietic system;

⑨Have a history of immunodeficiency (including but not limited to HIV positive test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation);

⑩ Combining diseases judged by other investigators that may affect the clinical manifestations of this study, or increase the risk of the study;

Those who have participated in clinical trials of other drugs or have taken other research drugs within the past 4 weeks;

Those who are known to have a history of allergy to the components of this medicine;

smoking history;

suffer from contraindications to the sampling method;

The investigator judged that the trial could not be completed.

5. Medication plan

The patients will be randomly assigned to the traditional Chinese medicine treatment group or the placebo group, and the subjects will take the test drug or placebo orally once a day in the morning and evening for 4 weeks (28 days). Before enrollment, all subjects will receive or maintain relevant baseline treatment according to the comprehensive evaluation of the pulmonary disease research doctor, and the basic treatment includes inhaled glucocorticoid (ICS, Inhaled Corticosteroid) or Beta2 receptor agonist.

Participants in the Yanghe compound group will receive 9.25 g of yanghetang granules or placebo granules twice a day for 4 weeks. The consumption method is soaked in 100 ml of boiling water, and taken after breakfast and dinner.

6. Observation indicators

(1) Safety indicators: blood routine, liver and kidney function, electrolytes, CRP, myocardial enzyme spectrum of myocardial infarction and other dynamic monitoring of ICS, Beta2 receptor agonists, Yanghe compound adverse reactions;

(2) Curative effect indicators:

ACT index: The main evaluation index for the improvement of asthma in clinical patients was the ACT score, which was used to evaluate the clinical effect of asthma control in the Jiawei Yanghe decoction group and the placebo group after 28 days of intervention.

Pulmonary function indicators: including FEV1 improvement rate, FVC improvement rate.

2. Results

2.1 Baseline data of included cases

From July 2017 to September 2019, a total of 101 patients were screened in this study, 37 patients did not meet the inclusion and exclusion criteria, 20 patients were unwilling to participate in the study, and finally 44 patients participated as volunteers in this study. clinical research. 44 cases were randomized, of which 24 were assigned to the experimental drug group and 20 to the control drug group. Among them, 23 people in the traditional Chinese medicine group completed a one-month drug intervention, and 19 people in the placebo group completed a one-month drug intervention. One person in the traditional Chinese medicine group and one in the placebo group stopped taking the drug on their own, and the others did not find any adjustment of the dosage. The subjects' baseline status was balanced with no significant differences in age, sex, height, weight, BMI, diabetes, hormone use, and hypertension.

The efficacy evaluation indicators in the trial period of this trial mainly focus on the following three indicators: the change value of the ACT score from the baseline, the change rate of the forced expiratory volume in one second (FEV1) from the baseline, and the forced vital capacity (FVC) from the baseline. rate of change. The baseline ACT scores and pulmonary function indicators are shown in Table 1, and there was no statistical difference between the two groups (see Table 1).

Table 1 Baseline ACT and lung function

Difference comparison based on Wilcoxon rank sum test

*-P<0.05

2.2 Primary clinical endpoint

The covariance showed that the average ACT score of the traditional Chinese medicine group was 3.484 points higher than that of the placebo group. At the test level of 0.05, it was considered that there was a statistically significant difference in the improvement of ACT between the two groups. As for the secondary indicators, the FVC Chinese medicine group increased by 2.417% compared with the placebo group, and the FEV1 Chinese medicine group increased by 3.979% compared with the placebo group. Compared with the placebo group, the FEV1/FVC Chinese medicine group increased by 2.209, the PEF Chinese medicine group increased by 4.555% compared with the placebo group, and the FeNO (Fractional Exhaled Nitric Oxide) Chinese medicine group increased by 16.63 (ppb) compared with the placebo group. All other indicators showed a trend of improvement, but did not show a statistical difference.

Table 2 Results of covariance analysis of efficacy indicators

3. Conclusion

In this randomized, double-blind, placebo-controlled clinical study, the baseline conditions of the two groups of subjects were balanced. Subject compliance was good, with only 2 (4.5%) not receiving the full 4 weeks of treatment. There were no adverse events that might be related, definitely related or could not be judged related to the treatment. In the test, the proportion of basic treatment regimens in the two groups was relatively balanced, and no significant changes were found in the basic treatment regimen during the test period, so it can be considered that the basic treatment has an equal impact on the changes in efficacy in the two groups. After 4 weeks of treatment, the ACT score of the traditional Chinese medicine group was significantly higher than that of the placebo group by 3.484 points (1.549, 5.418). The secondary index of FVC in the traditional Chinese medicine group was increased by 2.417% (-3.020, 7.859), and the FEV1 was increased by 3.979% (-2.650, 10.610), but no significant statistical difference was found. Based on the ACT index, we have reason to infer that Yang and Dingchuan Fuf plus basic therapy is effective and safe for asthma control and treatment, and it is expected to become a good program in the treatment and control of asthma. Although the secondary indicators FEV1 and FVC did not show a statistical difference, the Yanghe Dingchuan compound showed a trend of improvement compared with the placebo group.

Example 10 Basic experimental research on the treatment of asthma with Yanghe Dingchuan Recipe

1. Materials and methods

1. Preparation of experimental drugs

Yanghe compound was made into an ointment, dissolved and mixed, and administered according to 0.2ml/20g body weight. The concentration of the decoction is converted according to the daily dose for adults (refer to the pharmacological experimental method, the equivalent dose is converted from the ratio of animal body surface area: the dose for mice = the dose for humans × 9.1 times).

2. Establishment of animal models

Eighteen healthy female BALB/c mice, SPF grade, 6-8 weeks old, were reared adaptively for 1 week. Mice were given 100ul sensitization solution (OVA+PBS configured to 2mg/ml, and alum diluted to 1mg/ml, such as 10mg OVA+5ml PBS+5ml alum) on the 0th day and the 7th day respectively. ; On days 14-23, 3% OVA was given for nebulization, once every other day, for a total of 5 times of nebulization. On days 24-26 for 3 consecutive days, mice were anesthetized with ether every day and then administered 50ul 1mg/ml OVA (50ug) intranasally, once a day, and detected after anesthesia on the 28th day (see Figure 1).

3. Animal grouping and drug intervention

Eighteen mice were randomly divided into 3 groups of 6 mice each. The specific groups are: blank control group, asthma model group, and traditional Chinese medicine treatment group. All patients who received Yanghe decoction were given traditional Chinese medicine gavage treatment from the 14th day. The control group was given normal saline gavage treatment, once a day, 0.2ml each time. , for 14 consecutive days. On the 28th day, the animals were sacrificed (see Figure 1).

3. Evaluation:

Respiratory function test: All animals were anesthetized on the 28th day, the trachea was exposed, a transverse incision was made, and the endotracheal intubation was placed in a body tracing box. The Buxco invasive RC respiratory function test instrument was used to detect the gas under the gradient challenge of methacholine. tract hyperresponsiveness and lung compliance.

Inflammatory cell count: After the respiratory function test, the eyeballs were removed to collect blood, and a self-made sterile bronchoalveolar lavage tube was inserted into the mouse trachea, tied with silk thread, and the lung tissue was digested, homogenized, and extracted. Cell pellet The cells were resuspended with 0.1 ml of PBS containing 1% BSA, and the BALF white blood cells were counted by a MINDRAYBC-5300vet five-differential animal hemocytometer.

Lung histopathology: The collected posterior lobe of the right lung was fixed in 10% neutral formalin solution for 1 week, and then taken out, from low concentration to high concentration alcohol (75% alcohol-85% alcohol-95% alcohol-100% alcohol Alcohol) as a dehydrating agent in turn to remove the water in the tissue block. Remove the tissue block, place the tissue block in xylene until clear, and replace the alcohol in the tissue block. The transparent tissue block was placed in the melted paraffin, and then placed in a paraffin-dissolving box to keep warm. After the paraffin was completely immersed in the tissue block, embedding was performed. Fix the embedded wax block on a microtome, cut 5 μm thick slices, iron the cut slices in hot water, and then paste them on a glass slide, put them in a 45°C incubator, and dry them. Use xylene to remove paraffin from the sections, then dehydrate from high concentration to low concentration alcohol, and then add distilled water for hydration. They were stained with hematoxylin for 5 min, rinsed with tap water, air-dried, and differentiated with hydrochloric acid and ethanol for 30 sec. Rinse under running water for 30min, then put in distilled water again for 3-5min. After taking them out, they were immersed in 70% and 90% alcohol and dehydrated for 10 minutes each. Take it out and put it in eosin staining solution for 3 minutes, and then dehydrate it with absolute ethanol for 2 minutes, twice. Then put in xylene for 10min to make the slices transparent. Finally, the transparent sections were dripped with neutral gum, covered with a cover slip, mounted, and labeled. Using an 80I fluorescence phase contrast upright microscope in bright field, magnify 200 times, observe the HE-stained sections of mouse lung tissue, and select representative lung tissue structures for photography.

4. Statistical analysis

Measurement data are expressed as mean±SEM. Homogeneity of variance test was used for comparison between two groups, independent samples t test was used for normal distribution, and Mann-Whitney nonparametric test was used for non-normal distribution. One-way analysis of variance (One-Way ANOVA) was used for comparison among multiple groups, multiple comparisons of multiple sample means were used, LSD test was used for homogeneity of variance, and Games-Howell test was used for heterogeneity of variance. P<0.05 was considered statistically significant.

2. Results

Respiratory function test results: It was found that after stimulation with different concentrations of methacholine, the airway resistance of the mice in the model group increased significantly. Compared with the normal group, the three doses were statistically different, and the airway resistance decreased after Chinese medicine treatment. , compared with the blank group, only the high dose has a statistical difference (Figure 2): the lung compliance of the asthma model group was significantly reduced, and there were statistical differences between the three doses of 3.125, 6.25 and 12.5 compared with the normal group (P<0.05); after treatment with traditional Chinese medicine, the lung compliance of asthmatic mice was improved, and there was a statistical difference between the high dose and the model group (Note: Blank is the blank control group, AS is the disease model group, and AT is the traditional Chinese medicine. Group).

Inflammatory cell count: It was found (Table 3 and Figure 3-5) that the number of leukocytes in the lungs of the mice in the model group was significantly higher than that of the mice in the blank group, and the total and classified counts of leukocytes were statistically different. somewhat reduced. The eosinophils in the model group were significantly increased, and the total number of leukocytes, lymphocytes and eosinophils in the lungs of asthmatic mice were decreased after Chinese medicine treatment, and there were statistical differences (Note: Blank is a blank control group, Model is the disease model group, YH is the Yanghe Dingchuan ointment group).

Table 3 Leukocytes and differential counts in lung tissue of mice in each group

Note: (Mean±SE, n=6), *P<0.05, **P<0.01 compared with Blank; ^#P <0.05, ^## P<0.01 compared with Model.

Pathological results of lung tissue: The lung tissue of each group of mice was collected for HE staining, and observed under a light microscope (200 μm) (Figure 2): the bronchial and alveolar structures of the mice in the normal group were clear, the alveolar walls were smooth, and the bronchial morphology was normal; the model group The mice showed obvious inflammatory cell infiltration, epithelial cell hyperplasia, airway wall thickening and other pathological manifestations; after treatment with traditional Chinese medicine, the degree of inflammatory cell infiltration in asthmatic mice was improved compared with the model group, and the alveolar and bronchial structures tended to be normal (indicating that Blank was Blank control group, Model is the disease model group, YH is the traditional Chinese medicine group).

Our research shows that Yanghe Compound has a significant clinical effect in the treatment of bronchial asthma. By observing the effect of Yanghe Compound on the intervention of asthmatic mice, it is also found that Yanghe Compound can improve airway hyperresponsiveness and reduce inflammatory cells in the lungs of asthmatic mice. At the same time, it improves the infiltration of inflammatory cells, airway remodeling and mucosal hyperplasia in pulmonary alveolar histopathology, which proves that Yanghe Compound is a great potential asthma treatment formula.

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The above are only the preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, without departing from the principles of the present invention, several improvements and supplements can be made, and these improvements and supplements should also be considered as It is the protection scope of the present invention.

Claims

A traditional Chinese medicine composition for the treatment of asthma, characterized in that, the traditional Chinese medicine composition is composed of the following raw materials by weight: 4-5 parts of turtle glue, 4-5 parts of turtle shell glue, 2-4 parts of antler glue, Aconite 5-7 parts, Huang Jingzi 14-16 parts, Rehmannia glutinosa 8-10 parts, Xanthium 5-7 parts, Raw Astragalus 14-16 parts, Fried Codonopsis 7-8 parts, Xianlingpi 8-10 parts, Xian Lingpi 8-10 parts 5-7 parts of cogongrass, 4-6 parts of saponin, 14-16 parts of rehmannia, 14-16 parts of mother-of-pearl, 14-16 parts of dandelion, 14-16 parts of Hedyotis diffusa, 7-8 parts of gypsum, 5-7 parts of ginger charcoal, 4-5 parts of licorice.
Chinese medicine composition according to claim 1, is characterized in that, described Chinese medicine composition is made up of the following raw materials by weight: 4.5 parts of turtle glue, 4.5 parts of turtle glue, 3 parts of antler glue; 6 parts of aconite , 15 parts of Huang Jingzi, 9 parts of Rehmannia glutinosa, 6 parts of cocklebur, 15 parts of raw Astragalus, 7.5 parts of fried Codonopsis, 9 parts of Xianlingpi, 6 parts of Curcuma, 4.5 parts of Saponin, 15 parts of Rehmannia glutinosa, Mother of Pearl 15 parts, 15 parts dandelion, 15 parts Hedyotis diffusa, 7.5 parts gypsum, 6 parts ginger charcoal, 4.5 parts licorice.
The traditional Chinese medicine composition according to any one of claims 1-2, wherein the traditional Chinese medicine composition is prepared into a clinically acceptable pharmaceutical preparation according to a conventional preparation method of traditional Chinese medicine.
The traditional Chinese medicine composition according to claim 3, wherein the pharmaceutical preparation is a granule, a powder, a capsule, a tablet or an oral liquid.
The application of any one of the Chinese medicinal compositions of claims 1-2 in the preparation of a medicine for the treatment of asthma.
The application according to claim 5, wherein the asthma is Yang deficiency type asthma.
The application according to claim 6, wherein the asthma is a type of asthma with Yang deficiency, rheumatism and blood stasis syndrome.
A medicine for the treatment of asthma, characterized in that the medicine is made from the traditional Chinese medicine composition described in any one of claims 1-2 and a pharmaceutically acceptable adjuvant.
medicine according to claim 8, is characterized in that, the preparation method of described medicine comprises:

(1) get the raw material medicine and add water to decoct for 1-2 hours;

(2) Drain the juice, precipitate to get the clear liquid, add pharmaceutically acceptable adjuvants, and bottle for later use.